X-124366141-T-G

Position:

• chrX-124366141-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000371139.9(SH2D1A):​c.201+317T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.81 (25515 hom., 25683 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: SH2D1A ENST00000371139.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.985

Genes affected

SH2D1A (HGNC:10820): (SH2 domain containing 1A) This gene encodes a protein that plays a major role in the bidirectional stimulation of T and B cells. This protein contains an SH2 domain and a short tail. It associates with the signaling lymphocyte-activation molecule, thereby acting as an inhibitor of this transmembrane protein by blocking the recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to its docking site. This protein can also bind to other related surface molecules that are expressed on activated T, B and NK cells, thereby modifying signal transduction pathways in these cells. Mutations in this gene cause lymphoproliferative syndrome X-linked type 1 or Duncan disease, a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus, with symptoms including severe mononucleosis and malignant lymphoma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

STAG2 (HGNC:11355): (STAG2 cohesin complex component) The protein encoded by this gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Targeted inactivation of this gene results in chromatid cohesion defects and aneuploidy, suggesting that genetic disruption of cohesin is a cause of aneuploidy in human cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-124366141-T-G is Benign according to our data. Variant chrX-124366141-T-G is described in ClinVar as [Benign]. Clinvar id is 1278483.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2D1A	NM_002351.5	c.201+317T>G		intron_variant		ENST00000371139.9	NP_002342.1
SH2D1A	NM_001114937.3	c.201+317T>G		intron_variant			NP_001108409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D1A	ENST00000371139.9	c.201+317T>G		intron_variant		1	NM_002351.5	ENSP00000360181	P3

Frequencies

GnomAD3 genomes AF: 0.807 AC: 88394 AN: 109473 Hom.: 25515 Cov.: 21 AF XY: 0.809 AC XY: 25668 AN XY: 31725

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.735

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.799

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.807 AC: 88403 AN: 109526 Hom.: 25515 Cov.: 21 AF XY: 0.808 AC XY: 25683 AN XY: 31788

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.889

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.938

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.800

Alfa AF: 0.832 Hom.: 7223

Bravo AF: 0.808

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

Apr 30, 2020

This variant is associated with the following publications: (PMID: 23554038) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs2049995; hg19: chrX-123499991;