Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

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
More

Uncertain Significance

Not Met criteria codes 7
PS4 BA1 PM2 PP3 PP2 BS1 BP4

Evidence Links 0

Expert Panel

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)
Not Met criteria codes
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).
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).
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).
PP3
UCSC database indicates this site is highly conserved. However, SpliceAI does not predict an impact to splicing
PP2
Not applicable for SHOC2
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
Curation History
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