chr5-53070332-G-A

Variant names:

• chr5-53070332-G-A
• rs2303126
• NM_002203.4:c.2235+72G>A

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.2235+72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 1,488,422 control chromosomes in the GnomAD database, including 6,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (588 hom., cov: 33)
  • Exomes 𝑓: 0.083 (5710 hom.)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0960
• Publications: 5 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=-0.89).
• BP6: Variant 5-53070332-G-A is Benign according to our data. Variant chr5-53070332-G-A is described in ClinVar as Benign. ClinVar VariationId is 1255354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	NM_002203.4	MANE Select	c.2235+72G>A		intron	N/A	NP_002194.2
	ITGA2	NR_073103.2		n.2352+72G>A		intron	N/A
	ITGA2	NR_073104.2		n.2352+72G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.2235+72G>A		intron	N/A	ENSP00000296585.5
	ITGA2	ENST00000509814.5	TSL:1	n.2235+72G>A		intron	N/A	ENSP00000424397.1
	ITGA2	ENST00000509960.5	TSL:1	n.*350+72G>A		intron	N/A	ENSP00000424642.1

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11248 AN: 151724 Hom.: 586 Cov.: 33

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.0982

Gnomad FIN AF: 0.0851

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0762

GnomAD4 exome AF: 0.0827 AC: 110584 AN: 1336580 Hom.: 5710 AF XY: 0.0822 AC XY: 55183 AN XY: 671502

African (AFR) AF: 0.0280 AC: 861 AN: 30704

American (AMR) AF: 0.217 AC: 9505 AN: 43844

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2731 AN: 25052

East Asian (EAS) AF: 0.215 AC: 8312 AN: 38674

South Asian (SAS) AF: 0.0877 AC: 7243 AN: 82592

European-Finnish (FIN) AF: 0.0867 AC: 4594 AN: 52968

Middle Eastern (MID) AF: 0.0690 AC: 381 AN: 5522

European-Non Finnish (NFE) AF: 0.0720 AC: 72049 AN: 1001094

Other (OTH) AF: 0.0874 AC: 4908 AN: 56130

GnomAD4 genome AF: 0.0741 AC: 11254 AN: 151842 Hom.: 588 Cov.: 33 AF XY: 0.0760 AC XY: 5640 AN XY: 74180

African (AFR) AF: 0.0298 AC: 1237 AN: 41492

American (AMR) AF: 0.161 AC: 2459 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3464

East Asian (EAS) AF: 0.172 AC: 879 AN: 5106

South Asian (SAS) AF: 0.0983 AC: 473 AN: 4814

European-Finnish (FIN) AF: 0.0851 AC: 901 AN: 10590

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0701 AC: 4752 AN: 67826

Other (OTH) AF: 0.0802 AC: 169 AN: 2108

Alfa AF: 0.0663 Hom.: 61

Bravo AF: 0.0797

Asia WGS AF: 0.143 AC: 497 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.45
PhyloP100		-0.096
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: rs2303126; hg19: chr5-52366162; COSMIC: COSV56857588;