rs984966

Variant names:

• chr5-53073092-T-A
• rs984966
• NM_002203.4:c.2430-26T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-53073092-T-A
• chr5-53073092-T-C
• chr5-53073092-T-G

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.2430-26T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,604,542 control chromosomes in the GnomAD database, including 125,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10329 hom., cov: 31)
  • Exomes 𝑓: 0.39 (114901 hom.)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0720
• Publications: 6 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-53073092-T-A is Benign according to our data. Variant chr5-53073092-T-A is described in ClinVar as Benign. ClinVar VariationId is 1226263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002203.4. 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
	ITGA2	NM_002203.4	MANE Select	c.2430-26T>A		intron	N/A	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.2547-26T>A		intron	N/A
	ITGA2	NR_073104.2		n.2546+397T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.2430-26T>A		intron	N/A	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.2429+397T>A		intron	N/A	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.*545-26T>A		intron	N/A	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55555 AN: 151550 Hom.: 10330 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.376

GnomAD2 exomes AF: 0.387 AC: 96541 AN: 249334 AF XY: 0.386

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.386

Gnomad EAS exome AF: 0.299

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.386

GnomAD4 exome AF: 0.395 AC: 573752 AN: 1452872 Hom.: 114901 Cov.: 32 AF XY: 0.394 AC XY: 285031 AN XY: 723180

African (AFR) AF: 0.288 AC: 9562 AN: 33238

American (AMR) AF: 0.454 AC: 20227 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 10101 AN: 25992

East Asian (EAS) AF: 0.360 AC: 14203 AN: 39498

South Asian (SAS) AF: 0.366 AC: 31420 AN: 85948

European-Finnish (FIN) AF: 0.398 AC: 21119 AN: 53050

Middle Eastern (MID) AF: 0.381 AC: 2159 AN: 5668

European-Non Finnish (NFE) AF: 0.400 AC: 441670 AN: 1104972

Other (OTH) AF: 0.388 AC: 23291 AN: 59970

GnomAD4 genome AF: 0.366 AC: 55573 AN: 151670 Hom.: 10329 Cov.: 31 AF XY: 0.367 AC XY: 27188 AN XY: 74082

African (AFR) AF: 0.290 AC: 12008 AN: 41424

American (AMR) AF: 0.427 AC: 6495 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1280 AN: 3462

East Asian (EAS) AF: 0.306 AC: 1565 AN: 5114

South Asian (SAS) AF: 0.352 AC: 1690 AN: 4802

European-Finnish (FIN) AF: 0.398 AC: 4193 AN: 10534

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27061 AN: 67810

Other (OTH) AF: 0.376 AC: 792 AN: 2106

Alfa AF: 0.317 Hom.: 1462

Bravo AF: 0.367

Asia WGS AF: 0.333 AC: 1157 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.12
DANN	Benign	0.62
PhyloP100		-0.072
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs984966; hg19: chr5-52368922; COSMIC: COSV56864670;