Variant 1-156816018-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

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

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

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]

SH2D2A links:

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]

NTRK1 links:

Genome browser will be placed here

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 linkuse as main transcript	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 linkuse as main transcript	c.111G>C	p.Leu37=	synonymous_variant	2/9	1	NM_003975.4	ENSP00000357182	P2	Q9NP31-1

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

618

AN:

152154

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00405

AC:

617

AN:

152272

Hom.:

Cov.:

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.:

Bravo

AF:

0.00408

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00649

EpiControl

AF:

0.00789

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over