chr5-53083126-G-A

Variant names:

• chr5-53083126-G-A
• rs2303124
• NM_002203.4:c.3145-214G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002203.4(ITGA2):​c.3145-214G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,994 control chromosomes in the GnomAD database, including 3,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3865 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.644
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-53083126-G-A is Benign according to our data. Variant chr5-53083126-G-A is described in ClinVar as Benign. ClinVar VariationId is 1245438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 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.3145-214G>A		intron	N/A	NP_002194.2
	ITGA2	NR_073103.2		n.3159-214G>A		intron	N/A
	ITGA2	NR_073104.2		n.3120-214G>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.3145-214G>A		intron	N/A	ENSP00000296585.5
	ITGA2	ENST00000509814.5	TSL:1	n.*555-214G>A		intron	N/A	ENSP00000424397.1
	ITGA2	ENST00000509960.5	TSL:1	n.*1260-214G>A		intron	N/A	ENSP00000424642.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31268 AN: 151876 Hom.: 3858 Cov.: 32

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31281 AN: 151994 Hom.: 3865 Cov.: 32 AF XY: 0.207 AC XY: 15404 AN XY: 74270

African (AFR) AF: 0.0621 AC: 2575 AN: 41496

American (AMR) AF: 0.236 AC: 3604 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 935 AN: 3470

East Asian (EAS) AF: 0.0973 AC: 501 AN: 5148

South Asian (SAS) AF: 0.278 AC: 1335 AN: 4806

European-Finnish (FIN) AF: 0.282 AC: 2980 AN: 10550

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.274 AC: 18602 AN: 67960

Other (OTH) AF: 0.211 AC: 444 AN: 2108

Alfa AF: 0.249 Hom.: 2688

Bravo AF: 0.191

Asia WGS AF: 0.176 AC: 612 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

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	-0.85
CADD	Benign	3.8
DANN	Benign	0.35
PhyloP100		0.64
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: rs2303124; hg19: chr5-52378956; COSMIC: COSV56857903;