rs1833558

Variant names:

• chr5-53051731-G-A
• rs1833558
• NM_002203.4:c.779+172G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-53051731-G-A
• chr5-53051731-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002203.4(ITGA2):​c.779+172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,946 control chromosomes in the GnomAD database, including 10,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (10285 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.110
• Publications: 5 publications found

Genes affected

ITGA2 (HGNC:6137): (integrin subunit alpha 2) This gene encodes the alpha subunit of a transmembrane receptor for collagens and related proteins. The encoded protein forms a heterodimer with a beta subunit and mediates the adhesion of platelets and other cell types to the extracellular matrix. Loss of the encoded protein is associated with bleeding disorder platelet-type 9. Antibodies against this protein are found in several immune disorders, including neonatal alloimmune thrombocytopenia. This gene is located adjacent to a related alpha subunit gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ITGA2 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 9

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-53051731-G-A is Benign according to our data. Variant chr5-53051731-G-A is described in ClinVar as [Benign]. Clinvar id is 1281786.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.779+172G>A		intron_variant	Intron 7 of 29	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.779+172G>A		intron_variant	Intron 7 of 29	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55486 AN: 151826 Hom.: 10286 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.365 AC: 55507 AN: 151946 Hom.: 10285 Cov.: 32 AF XY: 0.366 AC XY: 27160 AN XY: 74268

African (AFR) AF: 0.290 AC: 12019 AN: 41468

American (AMR) AF: 0.427 AC: 6516 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1265 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1578 AN: 5172

South Asian (SAS) AF: 0.352 AC: 1696 AN: 4812

European-Finnish (FIN) AF: 0.396 AC: 4176 AN: 10542

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26981 AN: 67924

Other (OTH) AF: 0.374 AC: 787 AN: 2102

Alfa AF: 0.291 Hom.: 971

Bravo AF: 0.366

Asia WGS AF: 0.334 AC: 1159 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1833558; hg19: chr5-52347561;