dbSNP rs926103: SH2D2A:p.Asn52Ile (chr1-156815190-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003975.4(SH2D2A):c.155A>T(p.Asn52Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SH2D2A
NM_003975.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58

Publications

41 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046818048).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003975.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SH2D2A	NM_003975.4	MANE Select	c.155A>T	p.Asn52Ile	missense	Exon 3 of 9	NP_003966.2
SH2D2A	NM_001161441.2		c.155A>T	p.Asn52Ile	missense	Exon 3 of 9	NP_001154913.1
SH2D2A	NM_001161444.2		c.155A>T	p.Asn52Ile	missense	Exon 3 of 8	NP_001154916.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SH2D2A	ENST00000368199.8	TSL:1 MANE Select	c.155A>T	p.Asn52Ile	missense	Exon 3 of 9	ENSP00000357182.3
SH2D2A	ENST00000392306.2	TSL:1	c.155A>T	p.Asn52Ile	missense	Exon 3 of 9	ENSP00000376123.2
SH2D2A	ENST00000368198.8	TSL:1	c.101A>T	p.Asn34Ile	missense	Exon 3 of 9	ENSP00000357181.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1432450

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710780

African (AFR)

AF:

0.00

AC:

AN:

32582

American (AMR)

AF:

0.00

AC:

AN:

40934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24596

East Asian (EAS)

AF:

0.00

AC:

AN:

38490

South Asian (SAS)

AF:

0.00

AC:

AN:

82332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096570

Other (OTH)

AF:

0.00

AC:

AN:

59022

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.14

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.25

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.19

M_CAP

Benign

0.0024

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

PhyloP100

-1.6

PrimateAI

Benign

0.25

PROVEAN

Benign

0.14

REVEL

Benign

0.024

Sift

Benign

0.21

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.11

MutPred

0.27

Loss of loop (P = 0.0288)

MVP

0.34

MPC

0.32

ClinPred

0.12

GERP RS

-9.9

PromoterAI

-0.055

Neutral

(source)

Varity_R

0.078

gMVP

0.15

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over