Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_007373.3(SHOC2):c.10A>C (p.Ser4Arg)

Curation Version - 1.2
Curation History
JSON LD for Version 1.2

CA136657

40635 (ClinVar)

Gene: SHOC2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f8ec95a4-b09f-4a17-984e-06b4098449c2

Approved on: 2024-09-17

Published on: 2024-10-02

HGVS expressions

NM_007373.3:c.10A>C

NM_007373.3(SHOC2):c.10A>C (p.Ser4Arg)

NC_000010.11:g.110964368A>C

CM000672.2:g.110964368A>C

NC_000010.10:g.112724126A>C

CM000672.1:g.112724126A>C

NC_000010.9:g.112714116A>C

NG_028922.1:g.49826A>C

ENST00000265277.10:c.10A>C

ENST00000451838.2:c.-242-36047A>C

ENST00000480155.2:n.246A>C

ENST00000685059.1:c.10A>C

ENST00000685613.1:c.10A>C

ENST00000687592.1:n.309A>C

ENST00000688928.1:c.10A>C

ENST00000689118.1:c.10A>C

ENST00000689300.1:c.10A>C

ENST00000689997.1:c.-380-21260A>C

ENST00000691151.1:n.302A>C

ENST00000691369.1:c.10A>C

ENST00000691441.1:c.10A>C

ENST00000691903.1:c.10A>C

ENST00000692776.1:c.10A>C

ENST00000369452.9:c.10A>C

ENST00000265277.9:c.10A>C

ENST00000369452.8:c.10A>C

ENST00000480155.1:n.494A>C

ENST00000489390.1:n.56-36047A>C

ENST00000489783.1:n.388A>C

NM_001269039.1:c.10A>C

NM_001269039.2:c.10A>C

NM_001324336.1:c.10A>C

NM_001324337.1:c.10A>C

NR_136749.1:n.116-21260A>C

NM_007373.4:c.10A>C

NM_001269039.3:c.10A>C

NM_001324336.2:c.10A>C

NM_001324337.2:c.10A>C

NR_136749.2:n.55-21260A>C

Benign

BP5 BP4 BA1

BP2 PP3 PM2 BS1

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specification: ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SHOC2 Version 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.10A>C variant in the SHOC2 gene is a missense variant predicted to cause substitution of serine by arginine at amino acid 4 (p.Ser4Arg). The highest filtering allele frequency in gnomAD v4.1.0 is 0.2286% (124/59742 alleles) in the Admixed American population and therefore meets this criterion (BA1). The computational predictor tool REVEL gives a score of 0.113 and does not predict a damaging effect on SHOC2 function (BP4). This variant 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). In summary, this variant meets criteria to be classified as benign for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: BA1, BP4, BP5 (Specification Version 2.1, 09/17/2024)

BP5

The variant 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).

BP4

The computational predictor tool REVEL gives a score of 0.113 and does not predict a damaging effect on function (BP4)

BA1

The highest filtering allele frequency in gnomAD v4.1.0 is 0.2286% (124/59742 alleles) in the Admixed American population and therefore meets this criterion (BA1).

BP2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP3

The computational predictor tool REVEL gives a score of 0.113 and does not predict a damaging effect on function (BP4)

PM2

The highest filtering allele frequency in gnomAD v4.1.0 is 0.2286% (124/59742 alleles) in the Admixed American population (BA1).

BS1

The highest filtering allele frequency in gnomAD v4.1.0 is 0.2286% (124/59742 alleles) in the Admixed American population (BA1).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.