NM_002203.4:c.2236-62T>C

Variant names:

• chr5-53071876-T-C
• rs2287871
• NM_002203.4:c.2236-62T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002203.4(ITGA2):​c.2236-62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,152,200 control chromosomes in the GnomAD database, including 134,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (17322 hom., cov: 32)
  • Exomes 𝑓: 0.48 (117323 hom.)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.478
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-53071876-T-C is Benign according to our data. Variant chr5-53071876-T-C is described in ClinVar as Benign. ClinVar VariationId is 802121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.2236-62T>C		intron_variant	Intron 17 of 29	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.2236-62T>C		intron_variant	Intron 17 of 29	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72365 AN: 151648 Hom.: 17302 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.483 AC: 482889 AN: 1000434 Hom.: 117323 AF XY: 0.482 AC XY: 249084 AN XY: 516902

African (AFR) AF: 0.483 AC: 11964 AN: 24760

American (AMR) AF: 0.516 AC: 21531 AN: 41714

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 11419 AN: 22972

East Asian (EAS) AF: 0.397 AC: 14759 AN: 37152

South Asian (SAS) AF: 0.456 AC: 34435 AN: 75478

European-Finnish (FIN) AF: 0.451 AC: 23619 AN: 52324

Middle Eastern (MID) AF: 0.524 AC: 2559 AN: 4886

European-Non Finnish (NFE) AF: 0.489 AC: 340679 AN: 695984

Other (OTH) AF: 0.485 AC: 21924 AN: 45164

GnomAD4 genome AF: 0.477 AC: 72428 AN: 151766 Hom.: 17322 Cov.: 32 AF XY: 0.474 AC XY: 35156 AN XY: 74168

African (AFR) AF: 0.475 AC: 19686 AN: 41414

American (AMR) AF: 0.513 AC: 7805 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1649 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1691 AN: 5112

South Asian (SAS) AF: 0.438 AC: 2113 AN: 4820

European-Finnish (FIN) AF: 0.453 AC: 4791 AN: 10582

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33070 AN: 67828

Other (OTH) AF: 0.497 AC: 1050 AN: 2114

Alfa AF: 0.485 Hom.: 46512

Bravo AF: 0.484

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Platelet-type bleeding disorder 9 Benign:1

May 28, 2019

Mendelics

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	-0.83
CADD	Benign	3.2
DANN	Benign	0.70
PhyloP100		-0.48
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: rs2287871; hg19: chr5-52367706; COSMIC: COSV56857596;