1-156813865-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.550G>A​(p.Glu184Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,352,380 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: not found (cov: 33)
Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

SH2D2A
NM_003975.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.119
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]

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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=0.10122964).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH2D2ANM_003975.4 linkuse as main transcriptc.550G>A p.Glu184Lys missense_variant 5/9 ENST00000368199.8 NP_003966.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SH2D2AENST00000368199.8 linkuse as main transcriptc.550G>A p.Glu184Lys missense_variant 5/91 NM_003975.4 ENSP00000357182 P2Q9NP31-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000724
AC:
1
AN:
138056
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
74492
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000165
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.39e-7
AC:
1
AN:
1352380
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
661872
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.44e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000856
AC:
1

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 GeneticsJan 23, 2023The c.580G>A (p.E194K) alteration is located in exon 5 (coding exon 5) of the SH2D2A gene. This alteration results from a G to A substitution at nucleotide position 580, causing the glutamic acid (E) at amino acid position 194 to be replaced by a lysine (K). 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
0.097
BayesDel_addAF
Uncertain
0.022
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.32
.;T;.
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.82
T;T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Uncertain
-0.18
T
MutationAssessor
Benign
0.15
.;N;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.1
N;N;N
REVEL
Benign
0.27
Sift
Benign
0.045
D;D;T
Sift4G
Benign
0.13
T;T;T
Polyphen
0.82, 0.89
.;P;P
Vest4
0.11
MutPred
0.34
.;Gain of ubiquitination at E184 (P = 0.0109);.;
MVP
0.94
MPC
0.33
ClinPred
0.18
T
GERP RS
-1.4
Varity_R
0.11
gMVP
0.31

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: rs779033248; hg19: chr1-156783657; API