1-156815131-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003975.4(SH2D2A):​c.214G>A​(p.Ala72Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,609,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SH2D2A
NM_003975.4 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1762636).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH2D2ANM_003975.4 linkuse as main transcriptc.214G>A p.Ala72Thr missense_variant 3/9 ENST00000368199.8 NP_003966.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SH2D2AENST00000368199.8 linkuse as main transcriptc.214G>A p.Ala72Thr missense_variant 3/91 NM_003975.4 ENSP00000357182 P2Q9NP31-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152244
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000577
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:
0.0000164
AC:
4
AN:
243222
Hom.:
0
AF XY:
0.0000152
AC XY:
2
AN XY:
131460
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000224
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:
0.00000137
AC:
2
AN:
1457268
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
724686
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000508
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152362
Hom.:
0
Cov.:
33
AF XY:
0.0000268
AC XY:
2
AN XY:
74520
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3

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 GeneticsApr 19, 2023The c.214G>A (p.A72T) alteration is located in exon 3 (coding exon 3) of the SH2D2A gene. This alteration results from a G to A substitution at nucleotide position 214, causing the alanine (A) at amino acid position 72 to be replaced by a threonine (T). 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
0.12
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
22
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.50
.;T;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.77
T;T;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Uncertain
2.0
.;M;M
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.3
N;N;N
REVEL
Benign
0.15
Sift
Uncertain
0.0050
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.32
MutPred
0.36
.;Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP
0.89
MPC
0.64
ClinPred
0.70
D
GERP RS
4.5
Varity_R
0.094
gMVP
0.13

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

LitVar

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

Other links and lift over

dbSNP: rs544543274; hg19: chr1-156784923; API