Variant chr1-156807267-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_003975.4(SH2D2A):c.1081G>C(p.Ala361Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0024 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SH2D2A
NM_003975.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.169

Variant links:

Genes affected

SH2D2A (HGNC:10821): (SH2 domain containing 2A) This gene encodes an adaptor protein thought to function in T-cell signal transduction. A related protein in mouse is responsible for the activation of lymphocyte-specific protein-tyrosine kinase and functions in downstream signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

SH2D2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048122466).

BP6

Variant 1-156807267-C-G is Benign according to our data. Variant chr1-156807267-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2471514.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D2A	NM_003975.4 linkuse as main transcript	c.1081G>C	p.Ala361Pro	missense_variant	8/9	ENST00000368199.8	NP_003966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D2A	ENST00000368199.8 linkuse as main transcript	c.1081G>C	p.Ala361Pro	missense_variant	8/9	1	NM_003975.4	ENSP00000357182	P2	Q9NP31-1
SH2D2A	ENST00000392306.2 linkuse as main transcript	c.1111G>C	p.Ala371Pro	missense_variant	8/9	1		ENSP00000376123		Q9NP31-2
SH2D2A	ENST00000368198.7 linkuse as main transcript	c.1027G>C	p.Ala343Pro	missense_variant	8/9	1		ENSP00000357181	A2	Q9NP31-4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

53190

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000557

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000109

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000133

AC:

AN:

142480

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

80304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.000543

Gnomad FIN exome

AF:

0.000659

Gnomad NFE exome

AF:

0.0000395

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00239

AC:

481

AN:

200870

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

268

AN XY:

110426

show subpopulations

Gnomad4 AFR exome

AF:

0.000948

Gnomad4 AMR exome

AF:

0.00156

Gnomad4 ASJ exome

AF:

0.00154

Gnomad4 EAS exome

AF:

0.00112

Gnomad4 SAS exome

AF:

0.00371

Gnomad4 FIN exome

AF:

0.00373

Gnomad4 NFE exome

AF:

0.00231

Gnomad4 OTH exome

AF:

0.00256

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000132

AC:

AN:

53220

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

25496

show subpopulations

Gnomad4 AFR

AF:

0.000225

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000557

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000109

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000192

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.4

DANN

Benign

0.96

DEOGEN2

Benign

0.23

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0055

LIST_S2

Benign

0.28

T;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.90

.;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.060

N;N;N

REVEL

Benign

0.027

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.0, 0.0010

.;B;B

Vest4

0.097

MutPred

0.16

.;Gain of glycosylation at A361 (P = 0.0021);.;

MVP

0.56

MPC

0.33

ClinPred

0.033

GERP RS

0.46

Varity_R

0.067

gMVP

0.033

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