Genetic Variant SHOC2:c.1161+42T>C (chr10-111004836-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007373.4(SHOC2):c.1161+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 1,367,102 control chromosomes in the GnomAD database, including 463,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 52240 hom., cov: 31)

Exomes 𝑓: 0.82 ( 410815 hom. )

Consequence

SHOC2
NM_007373.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 10-111004836-T-C is Benign according to our data. Variant chr10-111004836-T-C is described in ClinVar as [Benign]. Clinvar id is 41450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOC2	NM_007373.4 link	c.1161+42T>C		intron_variant	Intron 5 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.1161+42T>C		intron_variant	Intron 5 of 8	1	NM_007373.4	ENSP00000358464.5		Q9UQ13-1

Frequencies

GnomAD3 genomes

AF:

0.828

AC:

125912

AN:

152064

Hom.:

52217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.830

Gnomad AMI

AF:

0.757

Gnomad AMR

AF:

0.880

Gnomad ASJ

AF:

0.851

Gnomad EAS

AF:

0.847

Gnomad SAS

AF:

0.815

Gnomad FIN

AF:

0.820

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.816

Gnomad OTH

AF:

0.815

GnomAD3 exomes

AF:

0.836

AC:

191454

AN:

228946

Hom.:

80140

AF XY:

0.833

AC XY:

103294

AN XY:

124032

show subpopulations

Gnomad AFR exome

AF:

0.831

Gnomad AMR exome

AF:

0.923

Gnomad ASJ exome

AF:

0.846

Gnomad EAS exome

AF:

0.844

Gnomad SAS exome

AF:

0.821

Gnomad FIN exome

AF:

0.817

Gnomad NFE exome

AF:

0.815

Gnomad OTH exome

AF:

0.828

GnomAD4 exome

AF:

0.822

AC:

999103

AN:

1214920

Hom.:

410815

Cov.:

AF XY:

0.822

AC XY:

505960

AN XY:

615354

show subpopulations

Gnomad4 AFR exome

AF:

0.834

Gnomad4 AMR exome

AF:

0.917

Gnomad4 ASJ exome

AF:

0.845

Gnomad4 EAS exome

AF:

0.862

Gnomad4 SAS exome

AF:

0.823

Gnomad4 FIN exome

AF:

0.814

Gnomad4 NFE exome

AF:

0.815

Gnomad4 OTH exome

AF:

0.825

GnomAD4 genome

AF:

0.828

AC:

125982

AN:

152182

Hom.:

52240

Cov.:

AF XY:

0.828

AC XY:

61626

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.830

Gnomad4 AMR

AF:

0.880

Gnomad4 ASJ

AF:

0.851

Gnomad4 EAS

AF:

0.847

Gnomad4 SAS

AF:

0.815

Gnomad4 FIN

AF:

0.820

Gnomad4 NFE

AF:

0.816

Gnomad4 OTH

AF:

0.807

Alfa

AF:

0.824

Hom.:

27165

Bravo

AF:

0.831

Asia WGS

AF:

0.790

AC:

2749

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 18, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Noonan syndrome-like disorder with loose anagen hair 1

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.65

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

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