rs3074455

Positions:

• chr13-110512281-TAA-T
• chr13-110512281-T-TA
• chr13-110512281-TAAA-T
• chr13-110512281-TA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.*101_*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 0.57 in 1,349,882 control chromosomes in the GnomAD database, including 202,731 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (22851 hom., cov: 0)
  • Exomes 𝑓: 0.57 (179880 hom.)
• Consequence: COL4A2 NM_001846.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.271

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 -16 ACMG points.

• BP6: Variant 13-110512281-TAA-T is Benign according to our data. Variant chr13-110512281-TAA-T is described in ClinVar as [Benign]. Clinvar id is 311201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.*101_*102del		3_prime_UTR_variant	48/48	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.*101_*102del		3_prime_UTR_variant	48/48	5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000648222.1	n.928_929del		non_coding_transcript_exon_variant	1/1
COL4A2	ENST00000650225.1	n.2895_2896del		non_coding_transcript_exon_variant	19/19

Frequencies

GnomAD3 genomes AF: 0.553 AC: 82697 AN: 149576 Hom.: 22831 Cov.: 0

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.572 AC: 686056 AN: 1200200 Hom.: 179880 AF XY: 0.569 AC XY: 333320 AN XY: 585618

Gnomad4 AFR exome AF: 0.568

Gnomad4 AMR exome AF: 0.557

Gnomad4 ASJ exome AF: 0.584

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.491

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.553 AC: 82763 AN: 149682 Hom.: 22851 Cov.: 0 AF XY: 0.546 AC XY: 39869 AN XY: 72960

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.567

Bravo AF: 0.556

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Porencephalic cyst Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 02, 2019

- -

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;