2-189133613-C-T

Position:

• chr2-189133613-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000393.5(COL5A2):​c.98-23164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,016 control chromosomes in the GnomAD database, including 50,072 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (50072 hom., cov: 31)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

Genes affected

COL5A2 (HGNC:2210): (collagen type V alpha 2 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.98-23164G>A		intron_variant		ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.-41-23164G>A		intron_variant			XP_011508875.1
COL5A2	XM_047443251.1	c.-41-23164G>A		intron_variant			XP_047299207.1
COL5A2	XM_047443252.1	c.-41-23164G>A		intron_variant			XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.98-23164G>A		intron_variant		1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.-533-23164G>A		intron_variant		5		ENSP00000482184.1
COL5A2	ENST00000649966.1	c.-41-23164G>A		intron_variant				ENSP00000496785.1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120182 AN: 151896 Hom.: 50067 Cov.: 31

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.791 AC: 120216 AN: 152016 Hom.: 50072 Cov.: 31 AF XY: 0.794 AC XY: 59030 AN XY: 74306

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.941

Gnomad4 NFE AF: 0.915

Gnomad4 OTH AF: 0.807

Alfa AF: 0.839 Hom.: 6520

Bravo AF: 0.765

Asia WGS AF: 0.823 AC: 2863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.90
DANN	Benign	0.49

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: rs6752781; hg19: chr2-189998339;