1-156816045-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_003975.4(SH2D2A):​c.84C>T​(p.Asp28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

SH2D2A
NM_003975.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.430
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 1-156816045-G-A is Benign according to our data. Variant chr1-156816045-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1176836.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.43 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH2D2ANM_003975.4 linkuse as main transcriptc.84C>T p.Asp28= synonymous_variant 2/9 ENST00000368199.8 NP_003966.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SH2D2AENST00000368199.8 linkuse as main transcriptc.84C>T p.Asp28= synonymous_variant 2/91 NM_003975.4 ENSP00000357182 P2Q9NP31-1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000119
AC:
30
AN:
251114
Hom.:
0
AF XY:
0.000133
AC XY:
18
AN XY:
135704
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.000398
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000278
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000114
AC:
167
AN:
1461804
Hom.:
0
Cov.:
34
AF XY:
0.000111
AC XY:
81
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.000230
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000206
Gnomad4 NFE exome
AF:
0.000125
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.000956
Alfa
AF:
0.000211
Hom.:
0
Bravo
AF:
0.000159
EpiCase
AF:
0.000327
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
3.9
DANN
Benign
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146503193; hg19: chr1-156785837; API