13-110503135-C-A

Position:

• chr13-110503135-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001846.4(COL4A2):​c.3892C>A​(p.Pro1298Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL4A2 NM_001846.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.16

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:40156): (COL4A2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.3892C>A	p.Pro1298Thr	missense_variant	42/48	ENST00000360467.7	NP_001837.2
COL4A2-AS1	NR_046583.1	n.187-207G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.3892C>A	p.Pro1298Thr	missense_variant	42/48	5	NM_001846.4	ENSP00000353654.5
COL4A2	ENST00000650225.1	n.1547C>A		non_coding_transcript_exon_variant	13/19
COL4A2-AS1	ENST00000417970.2	n.187-207G>T		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.3892C>A (p.P1298T) alteration is located in exon 42 (coding exon 41) of the COL4A2 gene. This alteration results from a C to A substitution at nucleotide position 3892, causing the proline (P) at amino acid position 1298 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.31	N
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.25
Sift	Uncertain	0.014	D
Sift4G	Benign	0.13	T
Polyphen		0.93	P
Vest4		0.21
MutPred		0.36		Gain of phosphorylation at P1298 (P = 0.0089);
MVP		0.91
MPC		0.98
ClinPred		0.71	D
GERP RS		4.6
Varity_R		0.15
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-111155482;