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]

Link to SEPIO compliant JSON-LD document

Variant: NM_007373.3(SHOC2):c.-1C>T

CA223027

40634 (ClinVar)

Gene: SHOC2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7390e608-04b8-42c9-b7d9-27c20be71622

Approved on: 2024-09-17

Published on: 2024-10-02

HGVS expressions

NM_007373.3:c.-1C>T

NM_007373.3(SHOC2):c.-1C>T

NC_000010.11:g.110964358C>T

CM000672.2:g.110964358C>T

NC_000010.10:g.112724116C>T

CM000672.1:g.112724116C>T

NC_000010.9:g.112714106C>T

NG_028922.1:g.49816C>T

ENST00000265277.10:c.-1C>T

ENST00000451838.2:c.-242-36057C>T

ENST00000480155.2:n.236C>T

ENST00000685059.1:c.-1C>T

ENST00000685613.1:c.-1C>T

ENST00000687592.1:n.299C>T

ENST00000688928.1:c.-1C>T

ENST00000689118.1:c.-1C>T

ENST00000689300.1:c.-1C>T

ENST00000689997.1:c.-380-21270C>T

ENST00000691151.1:n.292C>T

ENST00000691369.1:c.-1C>T

ENST00000691441.1:c.-1C>T

ENST00000691903.1:c.-1C>T

ENST00000692776.1:c.-1C>T

ENST00000369452.9:c.-1C>T

ENST00000265277.9:c.-1C>T

ENST00000369452.8:c.-1C>T

ENST00000480155.1:n.484C>T

ENST00000489390.1:n.56-36057C>T

ENST00000489783.1:n.378C>T

NM_001269039.1:c.-1C>T

NM_001269039.2:c.-1C>T

NM_001324336.1:c.-1C>T

NM_001324337.1:c.-1C>T

NR_136749.1:n.116-21270C>T

NM_007373.4:c.-1C>T

NM_001269039.3:c.-1C>T

NM_001324336.2:c.-1C>T

NM_001324337.2:c.-1C>T

NR_136749.2:n.55-21270C>T

Uncertain Significance

BS1 BP4 PM2 PS4 PP3 PP2 BA1

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.-1C>T variant in the SHOC2 gene is an intronic variant located in the 5' UTR, 1 base upstream from the first translated codon. The highest population minor allele frequency in gnomAD v4.1.0 is 0.01172% (7/59740 alleles) in the Latino/Admixed American population. (PM2_Supporting/BS1/BA1 are not met). This variant has been identified in 2 independent occurrences in patients with a clinical features of a RASopathy (PS4 not met; GeneDx, EGL internal data GTR Lab ID's: 26957, 500060; ClinVar SCV000209050.9, SCV000113449.7). In summary, this variant meets criteria to be classified as variant of uncertain significance for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: None (Specification Version 2.1, 09/17/2024)

BS1

The highest population minor allele frequency in gnomAD v4.1.0 is 0.01172% (7/59740 alleles) in the Latino/Admixed American population. (PM2_Supporting/BS1/BA1 are not met).

BP4

UCSC database indicates this site is highly conserved. However, SpliceAI does not predict an impact to splicing

PM2

The highest population minor allele frequency in gnomAD v4.1.0 is 0.01172% (7/59740 alleles) in the Latino/Admixed American population. (PM2_Supporting/BS1/BA1 are not met).

PS4

The c.-1C>T variant in SHOC2 has been identified in 2 independent occurrences in patients with clinical features of a RASopathy, however it's not clear if the variant would have a deleterious affect (PS4 not met; GeneDx, EGL internal data; ClinVar SCV000209050.9, SCV000113449.7).

PP3

UCSC database indicates this site is highly conserved. However, SpliceAI does not predict an impact to splicing

PP2

Not applicable for SHOC2

BA1

The highest population minor allele frequency in gnomAD v4.1.0 is 0.01172% (7/59740 alleles) in the Latino/Admixed American population. (PM2_Supporting/BS1/BA1 are not met).

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.