chr1-156816018-C-G
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_003975.4(SH2D2A):āc.111G>Cā(p.Leu37=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,613,916 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0041 ( 4 hom., cov: 32)
Exomes š: 0.0058 ( 35 hom. )
Consequence
SH2D2A
NM_003975.4 synonymous
NM_003975.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.72
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 -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 1-156816018-C-G is Benign according to our data. Variant chr1-156816018-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1176211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.72 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 4 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SH2D2A | NM_003975.4 | c.111G>C | p.Leu37= | synonymous_variant | 2/9 | ENST00000368199.8 | NP_003966.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SH2D2A | ENST00000368199.8 | c.111G>C | p.Leu37= | synonymous_variant | 2/9 | 1 | NM_003975.4 | ENSP00000357182 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00406 AC: 618AN: 152154Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00504 AC: 1264AN: 250772Hom.: 8 AF XY: 0.00520 AC XY: 705AN XY: 135530
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GnomAD4 exome AF: 0.00577 AC: 8432AN: 1461644Hom.: 35 Cov.: 34 AF XY: 0.00578 AC XY: 4202AN XY: 727112
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GnomAD4 genome AF: 0.00405 AC: 617AN: 152272Hom.: 4 Cov.: 32 AF XY: 0.00399 AC XY: 297AN XY: 74452
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | SH2D2A: BP4, BP7, BS2 - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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