1-156809289-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003975.4(SH2D2A):​c.916G>A​(p.Val306Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

SH2D2A
NM_003975.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.693
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0322344).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH2D2ANM_003975.4 linkuse as main transcriptc.916G>A p.Val306Met missense_variant 7/9 ENST00000368199.8 NP_003966.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SH2D2AENST00000368199.8 linkuse as main transcriptc.916G>A p.Val306Met missense_variant 7/91 NM_003975.4 ENSP00000357182 P2Q9NP31-1
SH2D2AENST00000392306.2 linkuse as main transcriptc.946G>A p.Val316Met missense_variant 7/91 ENSP00000376123 Q9NP31-2
SH2D2AENST00000368198.7 linkuse as main transcriptc.862G>A p.Val288Met missense_variant 7/91 ENSP00000357181 A2Q9NP31-4
SH2D2AENST00000468744.5 linkuse as main transcriptn.613G>A non_coding_transcript_exon_variant 3/32

Frequencies

GnomAD3 genomes
AF:
0.000283
AC:
43
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000941
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000676
AC:
17
AN:
251420
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.000738
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461850
Hom.:
0
Cov.:
33
AF XY:
0.0000289
AC XY:
21
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.000627
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000289
AC:
44
AN:
152320
Hom.:
0
Cov.:
32
AF XY:
0.000295
AC XY:
22
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.000962
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000164
Hom.:
0
Bravo
AF:
0.000314
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000906
AC:
11

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 16, 2021The c.946G>A (p.V316M) alteration is located in exon 7 (coding exon 7) of the SH2D2A gene. This alteration results from a G to A substitution at nucleotide position 946, causing the valine (V) at amino acid position 316 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.28
.;T;.
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.80
T;T;T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.032
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
.;N;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.25
N;N;N
REVEL
Benign
0.065
Sift
Uncertain
0.0020
D;D;D
Sift4G
Benign
0.073
T;T;T
Polyphen
0.85, 0.95
.;P;P
Vest4
0.078
MVP
0.63
MPC
0.61
ClinPred
0.039
T
GERP RS
1.6
Varity_R
0.062
gMVP
0.35

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.

Other links and lift over

dbSNP: rs142571523; hg19: chr1-156779081; API