chr1-156816018-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003975.4(SH2D2A):c.111G>C(p.Leu37Leu) 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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

hereditary sensory and autonomic neuropathy type 4
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
familial medullary thyroid carcinoma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NTRK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SH2D2A	NM_003975.4 link	c.111G>C	p.Leu37Leu	synonymous_variant	Exon 2 of 9	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.111G>C	p.Leu37Leu	synonymous_variant	Exon 2 of 9	1	NM_003975.4	ENSP00000357182.3		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

GnomAD2 exomes

AF:

0.00504

AC:

1264

AN:

250772

AF XY:

0.00520

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 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

African (AFR)

AF:

0.000717

AC:

AN:

33478

American (AMR)

AF:

0.00367

AC:

164

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00325

AC:

AN:

26114

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39690

South Asian (SAS)

AF:

0.00409

AC:

353

AN:

86212

European-Finnish (FIN)

AF:

0.00258

AC:

138

AN:

53398

Middle Eastern (MID)

AF:

0.0111

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00656

AC:

7293

AN:

1111898

Other (OTH)

AF:

0.00512

AC:

309

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

408

817

1225

1634

2042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00405

AC:

617

AN:

152272

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

297

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41550

American (AMR)

AF:

0.00379

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.00228

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00662

AC:

450

AN:

68018

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NTRK1: BS2; SH2D2A: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.73

(source)

DANN

Benign

0.68

PhyloP100

-1.7

PromoterAI

0.035

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr1-156816018-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over