VCV000448933.2 - ClinVar

NM_007373.4(SHOC2):c.613A>G (p.Thr205Ala)

Germline

Top reviewed classifications are shown here.

Submission summary:

1 submission

1 submitter

1 condition

Reviewed by expert panel

Likely benign

Apr 2017 by ClinGen RASopa… FDA Recognized Database

for Noonan syndrome and Noonan-related syndrome

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007373.4(SHOC2):c.613A>G (p.Thr205Ala)

Variation ID: 448933 Accession: VCV000448933.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q25.2 10: 110964971 (GRCh38) [ NCBI UCSC ] 10: 112724729 (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	Dec 19, 2017	Dec 11, 2022	Apr 18, 2017

HGVS

Nucleotide	Protein	Molecular consequence
NM_007373.4:c.613A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_031399.2:p.Thr205Ala	missense
NM_001269039.3:c.613A>G	NP_001255968.1:p.Thr205Ala	missense
NM_001324336.2:c.613A>G	NP_001311265.1:p.Thr205Ala	missense
NM_001324337.2:c.613A>G	NP_001311266.1:p.Thr205Ala	missense
NC_000010.11:g.110964971A>G
NC_000010.10:g.112724729A>G
NG_028922.1:g.50429A>G
LRG_753:g.50429A>G
LRG_753t1:c.613A>G	LRG_753p1:p.Thr205Ala

... more HGVS ... less HGVS

Protein change

T205A

Other names

NM_007373.3(SHOC2):c.613A>G

Canonical SPDI

NC_000010.11:110964970:A:G

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.

The Genome Aggregation Database (gnomAD), exomes 0.00005

Exome Aggregation Consortium (ExAC) 0.00009

Links

ClinGen: CA5689601 dbSNP: rs768411950 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.
SHOC2		No evidence available	No evidence available	GRCh38 GRCh37	515	553

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.
RASopathy	Likely benign (1)	reviewed by expert panel	Apr 18, 2017	RCV000521093.2

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.
Likely benign (Apr 18, 2017)	reviewed by expert panel (ClinGen RASopathy ACMG Specifications v1) Method: curation	Noonan syndrome and Noonan-related syndrome (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	ClinGen RASopathy Variant Curation Expert Panel FDA Recognized Database Accession: SCV000616496.4 First in ClinVar: Dec 19, 2017 Last updated: Dec 11, 2022	Other databases https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/795ea8ea-3f7d-49cf-b7e6-d4efa4eb47e5 Comment: The filtering allele frequency of the c.613A>G (p.Thr205Ala) variant in the SHOC2 gene is 0.0328% (10/16502) of South Asian chromosomes by the Exome Aggregation Consortium, … (more) The filtering allele frequency of the c.613A>G (p.Thr205Ala) variant in the SHOC2 gene is 0.0328% (10/16502) of South Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BS1; PMID:29493581) (less)

Comment:

The filtering allele frequency of the c.613A>G (p.Thr205Ala) variant in the SHOC2 gene is 0.0328% (10/16502) of South Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BS1; PMID:29493581)

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
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/795ea8ea-3f7d-49cf-b7e6-d4efa4eb47e5	-	-	-	-

Text-mined citations for rs768411950 ...

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 Dec 11, 2022

ClinVar Genomic variation as it relates to human health

NM_007373.4(SHOC2):c.613A>G (p.Thr205Ala)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs768411950 ...