5-53071876-T-G

Position:

• chr5-53071876-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002203.4(ITGA2):​c.2236-62T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,154,418 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00094 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (6 hom.)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.2236-62T>G		intron_variant		ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.2236-62T>G		intron_variant		1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.000936 AC: 142 AN: 151712 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000657

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00133

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00121 AC: 1211 AN: 1002588 Hom.: 6 AF XY: 0.00122 AC XY: 632 AN XY: 517884

Gnomad4 AFR exome AF: 0.000202

Gnomad4 AMR exome AF: 0.00156

Gnomad4 ASJ exome AF: 0.00857

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000556

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.00111

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome AF: 0.000935 AC: 142 AN: 151830 Hom.: 0 Cov.: 32 AF XY: 0.000822 AC XY: 61 AN XY: 74208

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000657

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00133

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00000425 Hom.: 27651

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.65

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: rs2287871; hg19: chr5-52367706;