chr5-52989837-G-C

Variant names:

• chr5-52989837-G-C
• rs40118
• NM_002203.4:c.64+305G>C

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.64+305G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 139,256 control chromosomes in the GnomAD database, including 36,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (36140 hom., cov: 24)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60
• Publications: 1 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-AS1 (HGNC:40306): (ITGA2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-52989837-G-C is Benign according to our data. Variant chr5-52989837-G-C is described in ClinVar as Benign. ClinVar VariationId is 1281037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.814 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.64+305G>C		intron	N/A	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.181+305G>C		intron	N/A
	ITGA2	NR_073104.2		n.181+305G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.64+305G>C		intron	N/A	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.64+305G>C		intron	N/A	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.64+305G>C		intron	N/A	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes AF: 0.744 AC: 103553 AN: 139154 Hom.: 36107 Cov.: 24

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.744 AC: 103640 AN: 139256 Hom.: 36140 Cov.: 24 AF XY: 0.746 AC XY: 50681 AN XY: 67928

African (AFR) AF: 0.653 AC: 24597 AN: 37686

American (AMR) AF: 0.788 AC: 11112 AN: 14100

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2279 AN: 3062

East Asian (EAS) AF: 0.650 AC: 3017 AN: 4640

South Asian (SAS) AF: 0.836 AC: 3809 AN: 4556

European-Finnish (FIN) AF: 0.772 AC: 7237 AN: 9376

Middle Eastern (MID) AF: 0.732 AC: 183 AN: 250

European-Non Finnish (NFE) AF: 0.786 AC: 49500 AN: 62966

Other (OTH) AF: 0.749 AC: 1411 AN: 1884

Alfa AF: 0.706 Hom.: 2890

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.24
PhyloP100		-1.6
PromoterAI		0.016	Neutral
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: rs40118; hg19: chr5-52285667;