5-53026891-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -1.02

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1262556.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA2	NM_002203.4	c.185+23G>T		intron_variant		ENST00000296585.10
LOC124900974	XR_007058767.1	n.132-411C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA2	ENST00000296585.10	c.185+23G>T		intron_variant		1	NM_002203.4	P1
	ENST00000652284.1	n.386-411C>A		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.292 AC: 72334 AN: 248068 Hom.: 10679 AF XY: 0.294 AC XY: 39457 AN XY: 134232

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 SAS exome AF: 0.273

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

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.314

Gnomad4 NFE exome AF: 0.304

Gnomad4 OTH exome AF: 0.300

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

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.282

Alfa AF: 0.315 Hom.: 7891

Bravo AF: 0.277

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.30
Dann	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs26678; hg19: chr5-52322721; COSMIC: COSV56866296;