Menu
GeneBe

1-156816018-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003975.4(SH2D2A):c.111G>C(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 (★).

Frequency

Genomes: 𝑓 0.0041 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0058 ( 35 hom. )

Consequence

SH2D2A
NM_003975.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.72
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 Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.72 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SH2D2ANM_003975.4 linkuse as main transcriptc.111G>C p.Leu37= synonymous_variant 2/9 ENST00000368199.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SH2D2AENST00000368199.8 linkuse as main transcriptc.111G>C p.Leu37= synonymous_variant 2/91 NM_003975.4 P2Q9NP31-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00406
AC:
618
AN:
152154
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00111
Gnomad AMI
AF:
0.00548
Gnomad AMR
AF:
0.00380
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.00217
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.00663
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00504
AC:
1264
AN:
250772
Hom.:
8
AF XY:
0.00520
AC XY:
705
AN XY:
135530
show subpopulations
Gnomad AFR exome
AF:
0.000802
Gnomad AMR exome
AF:
0.00402
Gnomad ASJ exome
AF:
0.00299
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00344
Gnomad FIN exome
AF:
0.00200
Gnomad NFE exome
AF:
0.00802
Gnomad OTH exome
AF:
0.00393
GnomAD4 exome
AF:
0.00577
AC:
8432
AN:
1461644
Hom.:
35
Cov.:
34
AF XY:
0.00578
AC XY:
4202
AN XY:
727112
show subpopulations
Gnomad4 AFR exome
AF:
0.000717
Gnomad4 AMR exome
AF:
0.00367
Gnomad4 ASJ exome
AF:
0.00325
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00409
Gnomad4 FIN exome
AF:
0.00258
Gnomad4 NFE exome
AF:
0.00656
Gnomad4 OTH exome
AF:
0.00512
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00405
AC:
617
AN:
152272
Hom.:
4
Cov.:
32
AF XY:
0.00399
AC XY:
297
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00111
Gnomad4 AMR
AF:
0.00379
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.00217
Gnomad4 NFE
AF:
0.00662
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00621
Hom.:
0
Bravo
AF:
0.00408
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00649
EpiControl
AF:
0.00789

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 TuebingenApr 01, 2024SH2D2A: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
Cadd
Benign
0.73
Dann
Benign
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs145574758; hg19: chr1-156785810; API