13-110473259-A-G

Position:

• chr13-110473259-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):​c.2425+109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,008,436 control chromosomes in the GnomAD database, including 124,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (17259 hom., cov: 34)
  • Exomes 𝑓: 0.50 (106888 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.389

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 13-110473259-A-G is Benign according to our data. Variant chr13-110473259-A-G is described in ClinVar as [Benign]. Clinvar id is 1293760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2425+109A>G		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2425+109A>G		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2	ENST00000494852.2	c.343+109A>G		intron_variant		3		ENSP00000497664.2

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72187 AN: 152032 Hom.: 17244 Cov.: 34

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.499 AC: 427139 AN: 856286 Hom.: 106888 AF XY: 0.500 AC XY: 216414 AN XY: 432594

Gnomad4 AFR exome AF: 0.453

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.533

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.495

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.505

Gnomad4 OTH exome AF: 0.507

GnomAD4 genome AF: 0.475 AC: 72238 AN: 152150 Hom.: 17259 Cov.: 34 AF XY: 0.474 AC XY: 35226 AN XY: 74352

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.500

Alfa AF: 0.489 Hom.: 2305

Bravo AF: 0.475

Asia WGS AF: 0.467 AC: 1626 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.5
DANN	Benign	0.32

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: rs11617206; hg19: chr13-111125606;