chr13-110502812-G-A

Position:

• chr13-110502812-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.3878-309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 295,046 control chromosomes in the GnomAD database, including 235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (118 hom., cov: 32)
  • Exomes 𝑓: 0.021 (117 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.367

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]

COL4A2-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-110502812-G-A is Benign according to our data. Variant chr13-110502812-G-A is described in ClinVar as [Benign]. Clinvar id is 1244807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.3878-309G>A		intron_variant		ENST00000360467.7	NP_001837.2
COL4A2-AS1	NR_046583.1	n.303C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.3878-309G>A		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2-AS1	ENST00000417970.2	n.303C>T		non_coding_transcript_exon_variant	3/3	3
COL4A2	ENST00000650225.1	n.1533-309G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2658 AN: 152166 Hom.: 118 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.0879

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00703

Gnomad OTH AF: 0.00764

GnomAD4 exome AF: 0.0213 AC: 3042 AN: 142762 Hom.: 117 Cov.: 0 AF XY: 0.0230 AC XY: 1720 AN XY: 74624

Gnomad4 AFR exome AF: 0.000713

Gnomad4 AMR exome AF: 0.00707

Gnomad4 ASJ exome AF: 0.00920

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.0476

Gnomad4 FIN exome AF: 0.0805

Gnomad4 NFE exome AF: 0.00706

Gnomad4 OTH exome AF: 0.0182

GnomAD4 genome AF: 0.0175 AC: 2658 AN: 152284 Hom.: 118 Cov.: 32 AF XY: 0.0221 AC XY: 1643 AN XY: 74446

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.0564

Gnomad4 FIN AF: 0.0879

Gnomad4 NFE AF: 0.00701

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0116 Hom.: 3

Bravo AF: 0.0105

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.63

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: rs74679761; hg19: chr13-111155159;