1-156815825-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001007792.1(NTRK1):c.-5G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,613,396 control chromosomes in the GnomAD database, including 370,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31223 hom., cov: 31)

Exomes 𝑓: 0.68 ( 338909 hom. )

Consequence

NTRK1
NM_001007792.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.84

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-156815825-G-A is Benign according to our data. Variant chr1-156815825-G-A is described in ClinVar as [Benign]. Clinvar id is 380853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-156815825-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2D2A	NM_003975.4 link	c.123+181C>T		intron_variant	Intron 2 of 8	ENST00000368199.8	NP_003966.2	Q9NP31-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2D2A	ENST00000368199.8 link	c.123+181C>T		intron_variant	Intron 2 of 8	1	NM_003975.4	ENSP00000357182.3		Q9NP31-1

Frequencies

GnomAD3 genomes

AF:

0.635

AC:

96440

AN:

151824

Hom.:

31197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.798

Gnomad AMR

AF:

0.695

Gnomad ASJ

AF:

0.683

Gnomad EAS

AF:

0.819

Gnomad SAS

AF:

0.646

Gnomad FIN

AF:

0.661

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.645

GnomAD3 exomes

AF:

0.674

AC:

169366

AN:

251274

Hom.:

57705

AF XY:

0.676

AC XY:

91790

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.499

Gnomad AMR exome

AF:

0.695

Gnomad ASJ exome

AF:

0.698

Gnomad EAS exome

AF:

0.818

Gnomad SAS exome

AF:

0.655

Gnomad FIN exome

AF:

0.649

Gnomad NFE exome

AF:

0.677

Gnomad OTH exome

AF:

0.669

GnomAD4 exome

AF:

0.679

AC:

992629

AN:

1461454

Hom.:

338909

Cov.:

AF XY:

0.679

AC XY:

493795

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.491

Gnomad4 AMR exome

AF:

0.693

Gnomad4 ASJ exome

AF:

0.689

Gnomad4 EAS exome

AF:

0.817

Gnomad4 SAS exome

AF:

0.657

Gnomad4 FIN exome

AF:

0.650

Gnomad4 NFE exome

AF:

0.682

Gnomad4 OTH exome

AF:

0.682

GnomAD4 genome

AF:

0.635

AC:

96511

AN:

151942

Hom.:

31223

Cov.:

AF XY:

0.640

AC XY:

47513

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.506

Gnomad4 AMR

AF:

0.696

Gnomad4 ASJ

AF:

0.683

Gnomad4 EAS

AF:

0.819

Gnomad4 SAS

AF:

0.647

Gnomad4 FIN

AF:

0.661

Gnomad4 NFE

AF:

0.677

Gnomad4 OTH

AF:

0.643

Alfa

AF:

0.668

Hom.:

70557

Bravo

AF:

0.635

Asia WGS

AF:

0.702

AC:

2441

AN:

3478

EpiCase

AF:

0.678

EpiControl

AF:

0.682

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 07, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

X-linked lymphoproliferative disease due to SH2D1A deficiency

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary insensitivity to pain with anhidrosis

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.50

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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