13-110457062-G-C

Position:

• chr13-110457062-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001846.4(COL4A2):​c.1340-281G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (2 hom., cov: 5)
  • Exomes 𝑓: 0.051 (1302 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0880

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-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 13-110457062-G-C is Benign according to our data. Variant chr13-110457062-G-C is described in ClinVar as [Benign]. Clinvar id is 1277278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0096 (375/39044) while in subpopulation NFE AF= 0.014 (255/18246). AF 95% confidence interval is 0.0126. There are 2 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. Median coverage is 5. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 375 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1340-281G>C		intron_variant		ENST00000360467.7	NP_001837.2
COL4A2-AS2	NR_171022.1	n.856C>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1340-281G>C		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2	ENST00000617564.2	c.596-281G>C		intron_variant		6		ENSP00000481492.3
COL4A2-AS2	ENST00000458403.2	n.856C>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.00961 AC: 375 AN: 39018 Hom.: 2 Cov.: 5

Gnomad AFR AF: 0.00556

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00467

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.0136

Gnomad FIN AF: 0.00315

Gnomad MID AF: 0.0333

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.00797

GnomAD3 exomes AF: 0.0289 AC: 2472 AN: 85396 Hom.: 172 AF XY: 0.0266 AC XY: 1265 AN XY: 47540

Gnomad AFR exome AF: 0.0568

Gnomad AMR exome AF: 0.0165

Gnomad ASJ exome AF: 0.0184

Gnomad EAS exome AF: 0.0148

Gnomad SAS exome AF: 0.0152

Gnomad FIN exome AF: 0.00585

Gnomad NFE exome AF: 0.0464

Gnomad OTH exome AF: 0.0362

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0509 AC: 9866 AN: 193994 Hom.: 1302 Cov.: 0 AF XY: 0.0447 AC XY: 5026 AN XY: 112448

Gnomad4 AFR exome AF: 0.0730

Gnomad4 AMR exome AF: 0.0234

Gnomad4 ASJ exome AF: 0.0762

Gnomad4 EAS exome AF: 0.0136

Gnomad4 SAS exome AF: 0.0357

Gnomad4 FIN exome AF: 0.0368

Gnomad4 NFE exome AF: 0.0631

Gnomad4 OTH exome AF: 0.0557

GnomAD4 genome AF: 0.00960 AC: 375 AN: 39044 Hom.: 2 Cov.: 5 AF XY: 0.00892 AC XY: 171 AN XY: 19160

Gnomad4 AFR AF: 0.00554

Gnomad4 AMR AF: 0.00466

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.00443

Gnomad4 SAS AF: 0.0136

Gnomad4 FIN AF: 0.00315

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.00784

Alfa AF: 0.127 Hom.: 9

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 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.55

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: rs28588005; hg19: chr13-111109409;