NM_007373.4(SHOC2):c.10A>C (p.Ser4Arg) AND RASopathy

Germline classification:: Benign (2 submissions)
Last evaluated:: Apr 3, 2017
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000518991.9

Allele description [Variation Report for NM_007373.4(SHOC2):c.10A>C (p.Ser4Arg)]

NM_007373.4(SHOC2):c.10A>C (p.Ser4Arg)

Gene:

SHOC2:SHOC2 leucine rich repeat scaffold protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q25.2

Genomic location:

Preferred name:

NM_007373.4(SHOC2):c.10A>C (p.Ser4Arg)

Other names:

p.S4R:AGT>CGT; NM_007373.3(SHOC2):c.10A>C

HGVS:

NC_000010.11:g.110964368A>C
NG_028922.1:g.49826A>C
NM_001269039.3:c.10A>C
NM_001324336.2:c.10A>C
NM_001324337.2:c.10A>C
NM_007373.4:c.10A>CMANE SELECT
NP_001255968.1:p.Ser4Arg
NP_001311265.1:p.Ser4Arg
NP_001311266.1:p.Ser4Arg
NP_031399.2:p.Ser4Arg
NP_031399.2:p.Ser4Arg
LRG_753t1:c.10A>C
LRG_753:g.49826A>C
LRG_753p1:p.Ser4Arg
NC_000010.10:g.112724126A>C
NM_007373.3:c.10A>C
c.10A>C

Protein change:

S4R

Links:

dbSNP: rs397517231

NCBI 1000 Genomes Browser:

rs397517231

Molecular consequence:

NM_001269039.3:c.10A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001324336.2:c.10A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001324337.2:c.10A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_007373.4:c.10A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: RASopathy
Synonyms:: rasopathies; Noonan spectrum disorder
Identifiers:: MONDO: MONDO:0021060; MedGen: C5555857

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000616429	ClinGen RASopathy Variant Curation Expert Panel	reviewed by expert panel (ClinGen RASopathy ACMG Specifications v1)	Benign (Apr 3, 2017)	germline	curation	Citation Link,
SCV001001390	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 13, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000616429

ClinGen RASopathy Variant Curation Expert Panel

reviewed by expert panel

(ClinGen RASopathy ACMG Specifications v1)

Benign
(Apr 3, 2017)

germline

curation

Citation Link,

SCV001001390

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 13, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From ClinGen RASopathy Variant Curation Expert Panel, SCV000616429.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

The c.10A>C variant in SHOC2 has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx, Partners LMM GTR Lab ID: 26957, 21766 internal data; ClinVar SCV000209046.7, SCV000062455.5). The filtering allele frequency of the c.10A>C (p.Ser4Arg) variant is 0.356% for Latino chromosomes by the Exome Aggregation Consortium (49/10712 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1). In summary, this variant meets criteria to be classified as benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BA1, BP5.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001001390.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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