Variant chr1-156815987-G-A details in Genebe, Genetics Data Aggregator

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+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,609,636 control chromosomes in the GnomAD database, including 373,314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32702 hom., cov: 31)

Exomes 𝑓: 0.68 ( 340612 hom. )

Consequence

SH2D2A
NM_003975.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.797

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:

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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=-0.9).

BP6

Variant 1-156815987-G-A is Benign according to our data. Variant chr1-156815987-G-A is described in ClinVar as [Benign]. Clinvar id is 667768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D2A	NM_003975.4 linkuse as main transcript	c.123+19C>T		intron_variant		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.123+19C>T		intron_variant		1	NM_003975.4	ENSP00000357182	P2	Q9NP31-1

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99054

AN:

151310

Hom.:

32670

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.793

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.818

Gnomad SAS

AF:

0.653

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.705

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.659

GnomAD3 exomes

AF:

0.676

AC:

167391

AN:

247594

Hom.:

56561

AF XY:

0.676

AC XY:

90447

AN XY:

133750

show subpopulations

Gnomad AFR exome

AF:

0.565

Gnomad AMR exome

AF:

0.693

Gnomad ASJ exome

AF:

0.697

Gnomad EAS exome

AF:

0.813

Gnomad SAS exome

AF:

0.657

Gnomad FIN exome

AF:

0.647

Gnomad NFE exome

AF:

0.673

Gnomad OTH exome

AF:

0.670

GnomAD4 exome

AF:

0.682

AC:

994688

AN:

1458206

Hom.:

340612

Cov.:

AF XY:

0.682

AC XY:

494642

AN XY:

725294

show subpopulations

Gnomad4 AFR exome

AF:

0.565

Gnomad4 AMR exome

AF:

0.696

Gnomad4 ASJ exome

AF:

0.689

Gnomad4 EAS exome

AF:

0.817

Gnomad4 SAS exome

AF:

0.662

Gnomad4 FIN exome

AF:

0.651

Gnomad4 NFE exome

AF:

0.683

Gnomad4 OTH exome

AF:

0.688

GnomAD4 genome

AF:

0.655

AC:

99137

AN:

151430

Hom.:

32702

Cov.:

AF XY:

0.658

AC XY:

48687

AN XY:

73954

show subpopulations

Gnomad4 AFR

AF:

0.575

Gnomad4 AMR

AF:

0.700

Gnomad4 ASJ

AF:

0.681

Gnomad4 EAS

AF:

0.817

Gnomad4 SAS

AF:

0.654

Gnomad4 FIN

AF:

0.660

Gnomad4 NFE

AF:

0.676

Gnomad4 OTH

AF:

0.657

Alfa

AF:

0.651

Hom.:

7137

Bravo

AF:

0.658

Asia WGS

AF:

0.708

AC:

2462

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary insensitivity to pain with anhidrosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.45

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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