1-156815825-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003975.4(SH2D2A):c.123+181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,613,396 control chromosomes in the GnomAD database, including 370,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.64 ( 31223 hom., cov: 31)
Exomes 𝑓: 0.68 ( 338909 hom. )
Consequence
SH2D2A
NM_003975.4 intron
NM_003975.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.84
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]
NTRK1 (HGNC:8031): (neurotrophic receptor tyrosine kinase 1) This gene encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated with congenital insensitivity to pain, anhidrosis, self-mutilating behavior, cognitive disability and cancer. Alternate transcriptional splice variants of this gene have been found, but only three have been characterized to date. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 1-156815825-G-A is Benign according to our data. Variant chr1-156815825-G-A is described in ClinVar as [Benign]. Clinvar id is 380853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-156815825-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SH2D2A | NM_003975.4 | c.123+181C>T | intron_variant | ENST00000368199.8 | NP_003966.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SH2D2A | ENST00000368199.8 | c.123+181C>T | intron_variant | 1 | NM_003975.4 | ENSP00000357182 | P2 |
Frequencies
GnomAD3 genomes AF: 0.635 AC: 96440AN: 151824Hom.: 31197 Cov.: 31
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GnomAD3 exomes AF: 0.674 AC: 169366AN: 251274Hom.: 57705 AF XY: 0.676 AC XY: 91790AN XY: 135806
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GnomAD4 exome AF: 0.679 AC: 992629AN: 1461454Hom.: 338909 Cov.: 57 AF XY: 0.679 AC XY: 493795AN XY: 727032
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GnomAD4 genome AF: 0.635 AC: 96511AN: 151942Hom.: 31223 Cov.: 31 AF XY: 0.640 AC XY: 47513AN XY: 74258
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 07, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
X-linked lymphoproliferative disease due to SH2D1A deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Hereditary insensitivity to pain with anhidrosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 08, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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DANN
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at