1-156815752-AC-A

Position:

• chr1-156815752-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003975.4(SH2D2A):​c.123+253del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,551,468 control chromosomes in the GnomAD database, including 212 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (121 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (91 hom.)
• Consequence: SH2D2A NM_003975.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-156815752-AC-A is Benign according to our data. Variant chr1-156815752-AC-A is described in ClinVar as [Benign]. Clinvar id is 1221990.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2D2A	NM_003975.4	c.123+253del		intron_variant		ENST00000368199.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2D2A	ENST00000368199.8	c.123+253del		intron_variant		1	NM_003975.4	P2

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3145 AN: 152134 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.00210 AC: 2936 AN: 1399216 Hom.: 91 Cov.: 25 AF XY: 0.00177 AC XY: 1236 AN XY: 699920

Gnomad4 AFR exome AF: 0.0685

Gnomad4 AMR exome AF: 0.00455

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000165

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000174

Gnomad4 OTH exome AF: 0.00489

GnomAD4 genome AF: 0.0207 AC: 3149 AN: 152252 Hom.: 121 Cov.: 32 AF XY: 0.0201 AC XY: 1500 AN XY: 74446

Gnomad4 AFR AF: 0.0714

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0153 Hom.: 10

Bravo AF: 0.0235

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 26, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs146775862; hg19: chr1-156785544;