Genetic Variant SHOC2:c.1541-7dupT (chr10-111011593-A-AT) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_007373.4(SHOC2):c.1541-7dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,530,892 control chromosomes in the GnomAD database, including 3 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00092 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

SHOC2
NM_007373.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

SHOC2 (HGNC:15454): (SHOC2 leucine rich repeat scaffold protein) This gene encodes a protein that consists almost entirely of leucine-rich repeats, a domain implicated in protein-protein interactions. The protein may function as a scaffold linking RAS to downstream signal transducers in the RAS/ERK MAP kinase signaling cascade. Mutations in this gene have been associated with Noonan-like syndrome with loose anagen hair. [provided by RefSeq, May 2010]

SHOC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 10-111011593-A-AT is Benign according to our data. Variant chr10-111011593-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 445472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 139 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOC2	NM_007373.4 link	c.1541-7dupT		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000369452.9	NP_031399.2	Q9UQ13-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOC2	ENST00000369452.9 link	c.1541-17_1541-16insT		intron_variant	Intron 8 of 8	1	NM_007373.4	ENSP00000358464.5		Q9UQ13-1

Frequencies

GnomAD3 genomes

AF:

0.000915

AC:

138

AN:

150754

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000927

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000418

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000488

Gnomad OTH

AF:

0.000964

GnomAD4 exome

AF:

0.00130

AC:

1794

AN:

1380020

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

845

AN XY:

689612

show subpopulations

Gnomad4 AFR exome

AF:

0.00297

Gnomad4 AMR exome

AF:

0.000685

Gnomad4 ASJ exome

AF:

0.000358

Gnomad4 EAS exome

AF:

0.000233

Gnomad4 SAS exome

AF:

0.000881

Gnomad4 FIN exome

AF:

0.000473

Gnomad4 NFE exome

AF:

0.00138

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.000921

AC:

139

AN:

150872

Hom.:

Cov.:

AF XY:

0.000964

AC XY:

AN XY:

73688

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.000926

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000419

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000489

Gnomad4 OTH

AF:

0.000954

Asia WGS

AF:

0.00144

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 23, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Apr 18, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

RASopathy

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Noonan syndrome and Noonan-related syndrome

Benign:1

Jun 01, 2019

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

10-111011593-ATT-ATTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over