chr13-110512281-TAAA-T

Position:

• chr13-110512281-TAAA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001846.4(COL4A2):​c.*100_*102del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,341,292 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000047 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00070 (1 hom.)
• Consequence: COL4A2 NM_001846.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000705 (840/1191538) while in subpopulation AMR AF= 0.00151 (28/18530). AF 95% confidence interval is 0.00107. There are 1 homozygotes in gnomad4_exome. There are 426 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.*100_*102del		3_prime_UTR_variant	48/48	ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.*100_*102del		3_prime_UTR_variant	48/48	5	NM_001846.4	P1
COL4A2	ENST00000648222.1	n.927_929del		non_coding_transcript_exon_variant	1/1
COL4A2	ENST00000650225.1	n.2894_2896del		non_coding_transcript_exon_variant	19/19

Frequencies

GnomAD3 genomes AF: 0.0000468 AC: 7 AN: 149648 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000743

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000705 AC: 840 AN: 1191538 Hom.: 1 AF XY: 0.000733 AC XY: 426 AN XY: 581290

Gnomad4 AFR exome AF: 0.00101

Gnomad4 AMR exome AF: 0.00151

Gnomad4 ASJ exome AF: 0.00121

Gnomad4 EAS exome AF: 0.000170

Gnomad4 SAS exome AF: 0.000878

Gnomad4 FIN exome AF: 0.000968

Gnomad4 NFE exome AF: 0.000670

Gnomad4 OTH exome AF: 0.000668

GnomAD4 genome AF: 0.0000467 AC: 7 AN: 149754 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73002

Gnomad4 AFR AF: 0.0000489

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000743

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs397838577; hg19: chr13-111164628;