1-156809448-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003975.4(SH2D2A):c.757C>T(p.Pro253Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,611,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
SH2D2A
NM_003975.4 missense
NM_003975.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 5.36
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=0.1818009).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SH2D2A | NM_003975.4 | c.757C>T | p.Pro253Ser | missense_variant | 7/9 | ENST00000368199.8 | NP_003966.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SH2D2A | ENST00000368199.8 | c.757C>T | p.Pro253Ser | missense_variant | 7/9 | 1 | NM_003975.4 | ENSP00000357182 | P2 | |
SH2D2A | ENST00000392306.2 | c.787C>T | p.Pro263Ser | missense_variant | 7/9 | 1 | ENSP00000376123 | |||
SH2D2A | ENST00000368198.7 | c.703C>T | p.Pro235Ser | missense_variant | 7/9 | 1 | ENSP00000357181 | A2 | ||
SH2D2A | ENST00000468744.5 | n.454C>T | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459498Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 725916
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74354
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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 | Nov 03, 2022 | The c.787C>T (p.P263S) alteration is located in exon 7 (coding exon 7) of the SH2D2A gene. This alteration results from a C to T substitution at nucleotide position 787, causing the proline (P) at amino acid position 263 to be replaced by a serine (S). 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
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
1.0
.;D;D
Vest4
MutPred
0.20
.;Gain of helix (P = 0.0034);.;
MVP
MPC
0.92
ClinPred
D
GERP RS
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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