1-156813931-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003975.4(SH2D2A):c.484C>T(p.Arg162Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,535,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
SH2D2A
NM_003975.4 missense
NM_003975.4 missense
Scores
1
11
7
Clinical Significance
Conservation
PhyloP100: 0.898
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SH2D2A | NM_003975.4 | c.484C>T | p.Arg162Trp | missense_variant | 5/9 | ENST00000368199.8 | NP_003966.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SH2D2A | ENST00000368199.8 | c.484C>T | p.Arg162Trp | missense_variant | 5/9 | 1 | NM_003975.4 | ENSP00000357182 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152254Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000359 AC: 5AN: 139412Hom.: 0 AF XY: 0.0000667 AC XY: 5AN XY: 74936
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GnomAD4 exome AF: 0.0000304 AC: 42AN: 1383482Hom.: 0 Cov.: 31 AF XY: 0.0000264 AC XY: 18AN XY: 682058
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74376
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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 submitter | clinical testing | Ambry Genetics | Aug 08, 2023 | The c.514C>T (p.R172W) alteration is located in exon 5 (coding exon 5) of the SH2D2A gene. This alteration results from a C to T substitution at nucleotide position 514, causing the arginine (R) at amino acid position 172 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;L;.
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;D
Vest4
MutPred
0.67
.;Gain of catalytic residue at A161 (P = 0.0363);.;
MVP
MPC
0.94
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at