chr1-156815979-A-G
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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+27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,608,350 control chromosomes in the GnomAD database, including 335,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.60 ( 27797 hom., cov: 32)
Exomes 𝑓: 0.65 ( 307322 hom. )
Consequence
SH2D2A
NM_003975.4 intron
NM_003975.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.31
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=-0.86).
BP6
Variant 1-156815979-A-G is Benign according to our data. Variant chr1-156815979-A-G is described in ClinVar as [Benign]. Clinvar id is 667767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH2D2A | NM_003975.4 | c.123+27T>C | intron_variant | ENST00000368199.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH2D2A | ENST00000368199.8 | c.123+27T>C | intron_variant | 1 | NM_003975.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.598 AC: 90538AN: 151320Hom.: 27774 Cov.: 32
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GnomAD3 exomes AF: 0.641 AC: 157680AN: 246056Hom.: 50693 AF XY: 0.643 AC XY: 85527AN XY: 133012
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GnomAD4 exome AF: 0.647 AC: 943044AN: 1456910Hom.: 307322 Cov.: 39 AF XY: 0.648 AC XY: 469662AN XY: 724586
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GnomAD4 genome AF: 0.598 AC: 90607AN: 151440Hom.: 27797 Cov.: 32 AF XY: 0.603 AC XY: 44603AN XY: 73952
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
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 | clinical testing | GeneDx | Jun 14, 2018 | 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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