VCV000094041.47 - ClinVar

NM_002206.3(ITGA7):c.2644G>A (p.Glu882Lys)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(10)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(5); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002206.3(ITGA7):c.2644G>A (p.Glu882Lys)

Variation ID: 94041 Accession: VCV000094041.47

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12q13.2 12: 55693209 (GRCh38) [ NCBI UCSC ] 12: 56086993 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 8, 2017	Oct 20, 2024	Aug 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_002206.3:c.2644G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002197.2:p.Glu882Lys	missense
NM_001144996.2:c.2656G>A	NP_001138468.1:p.Glu886Lys	missense
NM_001144997.2:c.2365G>A	NP_001138469.1:p.Glu789Lys	missense
NM_001367993.1:c.2317G>A	NP_001354922.1:p.Glu773Lys	missense
NM_001367994.1:c.1300G>A	NP_001354923.1:p.Glu434Lys	missense
NM_001374465.1:c.2626G>A	NP_001361394.1:p.Glu876Lys	missense
NM_001410977.1:c.2776G>A	NP_001397906.1:p.Glu926Lys	missense
NM_001414029.1:c.2638G>A	NP_001400958.1:p.Glu880Lys	missense
NM_001414030.1:c.2569G>A	NP_001400959.1:p.Glu857Lys	missense
NM_001414031.1:c.2557G>A	NP_001400960.1:p.Glu853Lys	missense
NM_001414032.1:c.2524G>A	NP_001400961.1:p.Glu842Lys	missense
NM_001414033.1:c.2461G>A	NP_001400962.1:p.Glu821Lys	missense
NM_001414034.1:c.2419G>A	NP_001400963.1:p.Glu807Lys	missense
NM_001414035.1:c.2305G>A	NP_001400964.1:p.Glu769Lys	missense
NC_000012.12:g.55693209C>T
NC_000012.11:g.56086993C>T
NG_012343.1:g.24097G>A
LRG_871:g.24097G>A
LRG_871t1:c.2644G>A	LRG_871p1:p.Glu882Lys
LRG_871t2:c.2365G>A	LRG_871p2:p.Glu789Lys

... more HGVS ... less HGVS

Protein change

E882K, E789K, E886K, E434K, E773K, E876K, E926K, E853K, E769K, E807K, E842K, E857K, E880K, E821K

Other names

Canonical SPDI

NC_000012.12:55693208:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00120 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.00109

1000 Genomes Project 0.00120

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00277

The Genome Aggregation Database (gnomAD) 0.00347

Trans-Omics for Precision Medicine (TOPMed) 0.00383

Exome Aggregation Consortium (ExAC) 0.00401

The Genome Aggregation Database (gnomAD), exomes 0.00426

Links

ClinGen: CA147560 dbSNP: rs144983062 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ITGA7		-	-	GRCh38 GRCh37	835	989

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Conflicting interpretations of pathogenicity (3)	criteria provided, conflicting classifications	Dec 5, 2017	RCV000079985.22
not provided	Likely benign (3)	criteria provided, single submitter	Aug 1, 2024	RCV000531646.32
Congenital muscular dystrophy due to integrin alpha-7 deficiency	Benign (3)	criteria provided, multiple submitters, no conflicts	Jan 29, 2024	RCV000988860.20
ITGA7-related disorder	Likely benign (1)	no assertion criteria provided	Nov 18, 2019	RCV003905050.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Mar 28, 2016)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000539398.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Comment: Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more) Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant reported in homozygous state in individual with congenital fiber-type disproportion - individual had hypotonia but pulmonary phenotypes were not reported. However, variant has high frequency, 5 homozygotes are present in ExAC, and Emory classifies as benign. (less) Method: Genome/Exome Filtration
Benign (Dec 05, 2017)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000513295.3 First in ClinVar: Mar 08, 2017 Last updated: Apr 09, 2018	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Aug 21, 2013)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000111876.8 First in ClinVar: Jan 17, 2014 Last updated: Apr 09, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ITGA7 Number of individuals with the variant: 2 Sex: mixed
Benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Congenital muscular dystrophy due to integrin alpha-7 deficiency Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001138752.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (Mar 19, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Congenital muscular dystrophy due to integrin alpha-7 deficiency Affected status: yes Allele origin: germline	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital Accession: SCV001984230.1 First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021
Benign (Jan 29, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Congenital muscular dystrophy due to integrin alpha-7 deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000648323.8 First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024
Likely benign (Aug 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001148760.27 First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024	Comment: ITGA7: BP4, BS2 Number of individuals with the variant: 22
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001964413.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021
Likely benign (Nov 18, 2019)	no assertion criteria provided Method: clinical testing	ITGA7-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004726625.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Study: VKGL Data-share Consensus Accession: SCV001800624.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021

Comment:

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant reported in homozygous state in individual with congenital fiber-type disproportion - individual had hypotonia but pulmonary phenotypes were not reported. However, variant has high frequency, 5 homozygotes are present in ExAC, and Emory classifies as benign.

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ITGA7	-	-	-	-

Text-mined citations for rs144983062 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_002206.3(ITGA7):c.2644G>A (p.Glu882Lys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs144983062 ...