chr5-53026891-G-T

Variant names:

• chr5-53026891-G-T
• rs26678
• NM_002203.4:c.185+23G>T

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.185+23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,592,920 control chromosomes in the GnomAD database, including 71,837 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6091 hom., cov: 32)
  • Exomes 𝑓: 0.30 (65746 hom.)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.02
• Publications: 10 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

ENSG00000286048 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-53026891-G-T is Benign according to our data. Variant chr5-53026891-G-T is described in ClinVar as Benign. ClinVar VariationId is 1262556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 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.185+23G>T		intron	N/A	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.302+23G>T		intron	N/A
	ITGA2	NR_073104.2		n.302+23G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.185+23G>T		intron	N/A	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.185+23G>T		intron	N/A	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.185+23G>T		intron	N/A	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42456 AN: 151940 Hom.: 6090 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.292 AC: 72334 AN: 248068 AF XY: 0.294

Gnomad AFR exome AF: 0.223

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.245

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.299 AC: 431379 AN: 1440864 Hom.: 65746 Cov.: 27 AF XY: 0.300 AC XY: 215145 AN XY: 717868

African (AFR) AF: 0.217 AC: 7192 AN: 33102

American (AMR) AF: 0.278 AC: 12386 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 9606 AN: 25950

East Asian (EAS) AF: 0.231 AC: 9103 AN: 39466

South Asian (SAS) AF: 0.273 AC: 23329 AN: 85536

European-Finnish (FIN) AF: 0.314 AC: 16712 AN: 53264

Middle Eastern (MID) AF: 0.387 AC: 2186 AN: 5650

European-Non Finnish (NFE) AF: 0.304 AC: 332979 AN: 1093676

Other (OTH) AF: 0.300 AC: 17886 AN: 59712

GnomAD4 genome AF: 0.279 AC: 42465 AN: 152056 Hom.: 6091 Cov.: 32 AF XY: 0.279 AC XY: 20735 AN XY: 74316

African (AFR) AF: 0.226 AC: 9369 AN: 41484

American (AMR) AF: 0.274 AC: 4182 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1332 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1297 AN: 5182

South Asian (SAS) AF: 0.283 AC: 1362 AN: 4820

European-Finnish (FIN) AF: 0.307 AC: 3247 AN: 10562

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.305 AC: 20698 AN: 67962

Other (OTH) AF: 0.282 AC: 595 AN: 2108

Alfa AF: 0.309 Hom.: 9844

Bravo AF: 0.277

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.87
CADD	Benign	0.30
DANN	Benign	0.60
PhyloP100		-1.0
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: rs26678; hg19: chr5-52322721; COSMIC: COSV56866296;