VCV000585948.18 - ClinVar

NM_201525.4(ADGRG1):c.14C>T (p.Ser5Leu)

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.

(6)

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(4); 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_201525.4(ADGRG1):c.14C>T (p.Ser5Leu)

Variation ID: 585948 Accession: VCV000585948.18

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16q21 16: 57650301 (GRCh38) [ NCBI UCSC ] 16: 57684213 (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	Oct 20, 2018	May 1, 2024	Jan 29, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_201525.4:c.14C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_958933.1:p.Ser5Leu	missense
NM_001145770.3:c.14C>T	NP_001139242.1:p.Ser5Leu	missense
NM_001145771.3:c.14C>T	NP_001139243.1:p.Ser5Leu	missense
NM_001145772.3:c.14C>T	NP_001139244.1:p.Ser5Leu	missense
NM_001145773.3:c.14C>T	NP_001139245.1:p.Ser5Leu	missense
NM_001145774.3:c.14C>T	NP_001139246.1:p.Ser5Leu	missense
NM_001290142.2:c.14C>T	NP_001277071.1:p.Ser5Leu	missense
NM_001290143.2:c.-469C>T		5 prime UTR
NM_001290144.2:c.-469C>T		5 prime UTR
NM_001370428.1:c.14C>T	NP_001357357.1:p.Ser5Leu	missense
NM_001370429.1:c.14C>T	NP_001357358.1:p.Ser5Leu	missense
NM_001370430.1:c.14C>T	NP_001357359.1:p.Ser5Leu	missense
NM_001370431.1:c.14C>T	NP_001357360.1:p.Ser5Leu	missense
NM_001370432.1:c.14C>T	NP_001357361.1:p.Ser5Leu	missense
NM_001370433.1:c.14C>T	NP_001357362.1:p.Ser5Leu	missense
NM_001370434.1:c.14C>T	NP_001357363.1:p.Ser5Leu	missense
NM_001370435.1:c.14C>T	NP_001357364.1:p.Ser5Leu	missense
NM_001370436.1:c.14C>T	NP_001357365.1:p.Ser5Leu	missense
NM_001370437.1:c.14C>T	NP_001357366.1:p.Ser5Leu	missense
NM_001370438.1:c.14C>T	NP_001357367.1:p.Ser5Leu	missense
NM_001370439.1:c.14C>T	NP_001357368.1:p.Ser5Leu	missense
NM_001370440.1:c.14C>T	NP_001357369.1:p.Ser5Leu	missense
NM_001370441.1:c.14C>T	NP_001357370.1:p.Ser5Leu	missense
NM_001370442.1:c.14C>T	NP_001357371.1:p.Ser5Leu	missense
NM_001370451.1:c.-469C>T		5 prime UTR
NM_001370453.1:c.-553C>T		5 prime UTR
NM_001370454.1:c.-414-946C>T		intron variant
NM_005682.7:c.14C>T	NP_005673.3:p.Ser5Leu	missense
NM_201524.4:c.14C>T	NP_958932.1:p.Ser5Leu	missense
NC_000016.10:g.57650301C>T
NC_000016.9:g.57684213C>T
NG_011643.1:g.35304C>T

... more HGVS ... less HGVS

Protein change

S5L

Other names

Canonical SPDI

NC_000016.10:57650300: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.

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

Exome Aggregation Consortium (ExAC) 0.00015

The Genome Aggregation Database (gnomAD), exomes 0.00017

The Genome Aggregation Database (gnomAD) 0.00033

Trans-Omics for Precision Medicine (TOPMed) 0.00039

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00069

Links

dbSNP: rs147879224 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.
ADGRG1		-	-	GRCh38 GRCh37	944	972

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 provided	Conflicting interpretations of pathogenicity (3)	criteria provided, conflicting classifications	Jan 29, 2024	RCV000711839.16
Bilateral frontoparietal polymicrogyria	Uncertain significance (2)	criteria provided, single submitter	Mar 2, 2018	RCV001116136.6
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Nov 1, 2023	RCV004026814.1

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 (Jan 25, 2018)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV000842244.1 First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018
Uncertain significance (Jun 13, 2018)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000861954.1 First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ADGRG1 Number of individuals with the variant: 1 Sex: mixed
Uncertain significance (Mar 02, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Bilateral frontoparietal polymicrogyria Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001274172.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
Likely benign (Jan 29, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001629621.4 First in ClinVar: May 23, 2021 Last updated: Feb 14, 2024
Uncertain significance (Nov 01, 2023)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV004859811.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Comment: The c.14C>T (p.S5L) alteration is located in exon 3 (coding exon 1) of the ADGRG1 gene. This alteration results from a C to T substitution … (more) The c.14C>T (p.S5L) alteration is located in exon 3 (coding exon 1) of the ADGRG1 gene. This alteration results from a C to T substitution at nucleotide position 14, causing the serine (S) at amino acid position 5 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
Uncertain significance (Jan 17, 2020)	no assertion criteria provided Method: clinical testing	Bilateral frontoparietal polymicrogyria Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001462688.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

Comment:

The c.14C>T (p.S5L) alteration is located in exon 3 (coding exon 1) of the ADGRG1 gene. This alteration results from a C to T substitution at nucleotide position 14, causing the serine (S) at amino acid position 5 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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=ADGRG1	-	-	-	-

Text-mined citations for rs147879224 ...

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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_201525.4(ADGRG1):c.14C>T (p.Ser5Leu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs147879224 ...