chr13-110503016-G-A

Position:

• chr13-110503016-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.3878-105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,034,966 control chromosomes in the GnomAD database, including 504,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68640 hom., cov: 35)
  • Exomes 𝑓: 0.99 (436260 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.500

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=-0.99).
• BP6: Variant 13-110503016-G-A is Benign according to our data. Variant chr13-110503016-G-A is described in ClinVar as [Benign]. Clinvar id is 1250227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.3878-105G>A		intron_variant		ENST00000360467.7	NP_001837.2
COL4A2-AS1	NR_046583.1	n.187-88C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.3878-105G>A		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2-AS1	ENST00000417970.2	n.187-88C>T		intron_variant		3
COL4A2	ENST00000650225.1	n.1533-105G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.946 AC: 144006 AN: 152210 Hom.: 68597 Cov.: 35

Gnomad AFR AF: 0.813

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.964

GnomAD4 exome AF: 0.994 AC: 877178 AN: 882638 Hom.: 436260 Cov.: 11 AF XY: 0.995 AC XY: 452183 AN XY: 454654

Gnomad4 AFR exome AF: 0.809

Gnomad4 AMR exome AF: 0.989

Gnomad4 ASJ exome AF: 0.983

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.985

GnomAD4 genome AF: 0.946 AC: 144105 AN: 152328 Hom.: 68640 Cov.: 35 AF XY: 0.948 AC XY: 70608 AN XY: 74496

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.983

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.964

Alfa AF: 0.981 Hom.: 22665

Bravo AF: 0.939

Asia WGS AF: 0.987 AC: 3433 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	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.52

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: rs406174; hg19: chr13-111155363;