rs148700291

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000360027.5(SH2D1A):c.-124T>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 0.00101 in 792,860 control chromosomes in the GnomAD database, including 1 homozygotes. There are 219 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., 18 hem., cov: 23)

Exomes 𝑓: 0.0010 ( 1 hom. 201 hem. )

Consequence

SH2D1A
ENST00000360027.5 5_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.361

Publications

0 publications found

Variant links:

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]

SH2D1A links:

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]

STAG2 Gene-Disease associations (from GenCC):

Mullegama-Klein-Martinez syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae)
Xq25 microduplication syndrome
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

STAG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant X-124346519-T-A is Benign according to our data. Variant chrX-124346519-T-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 367869.

BS2

High Hemizygotes in GnomAd4 at 18 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360027.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D1A	NM_002351.5	MANE Select	c.-124T>A		upstream_gene	N/A	NP_002342.1	O60880-1
	SH2D1A	NM_001114937.3		c.-124T>A		upstream_gene	N/A	NP_001108409.1	O60880-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SH2D1A	ENST00000360027.5	TSL:1	c.-124T>A	5_prime_UTR	Exon 1 of 4	ENSP00000353126.4	O60880-4
SH2D1A	ENST00000698113.1		c.-124T>A	5_prime_UTR	Exon 2 of 5	ENSP00000513571.1	O60880-1
SH2D1A	ENST00000698116.1		c.-59+33T>A	intron	N/A	ENSP00000513572.1	O60880-1

Frequencies

GnomAD3 genomes

AF:

0.000884

AC:

AN:

111995

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000163

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.000664

GnomAD4 exome

AF:

0.00103

AC:

704

AN:

680811

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

201

AN XY:

195465

show subpopulations

African (AFR)

AF:

0.000271

AC:

AN:

18425

American (AMR)

AF:

0.000437

AC:

AN:

34302

Ashkenazi Jewish (ASJ)

AF:

0.0000601

AC:

AN:

16636

East Asian (EAS)

AF:

0.00

AC:

AN:

27943

South Asian (SAS)

AF:

0.00

AC:

AN:

45298

European-Finnish (FIN)

AF:

0.000653

AC:

AN:

35225

Middle Eastern (MID)

AF:

0.00124

AC:

AN:

2414

European-Non Finnish (NFE)

AF:

0.00134

AC:

626

AN:

468266

Other (OTH)

AF:

0.000960

AC:

AN:

32302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000884

AC:

AN:

112049

Hom.:

Cov.:

AF XY:

0.000526

AC XY:

AN XY:

34235

show subpopulations

African (AFR)

AF:

0.000227

AC:

AN:

30850

American (AMR)

AF:

0.000471

AC:

AN:

10624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.00

AC:

AN:

3555

South Asian (SAS)

AF:

0.00

AC:

AN:

2704

European-Finnish (FIN)

AF:

0.000163

AC:

AN:

6147

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.00160

AC:

AN:

53104

Other (OTH)

AF:

0.000656

AC:

AN:

1524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000926

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

X-linked lymphoproliferative disease due to SH2D1A deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.9

(source)

DANN

Benign

0.80

PhyloP100

0.36

PromoterAI

-0.082

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over