rs10165260

chr2-189087906-G-Achr2-189087906-G-Cchr2-189087906-G-T

Variant summary

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

The NM_000393.5(COL5A2):c.645+789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 151,690 control chromosomes in the GnomAD database, including 57,508 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 0.86 (57508 hom., cov: 31)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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 = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A2	NM_000393.5	c.645+789C>T		intron_variant		ENST00000374866.9
COL5A2	XM_011510573.4	c.507+789C>T		intron_variant
COL5A2	XM_047443251.1	c.507+789C>T		intron_variant
COL5A2	XM_047443252.1	c.507+789C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A2	ENST00000374866.9	c.645+789C>T		intron_variant		1	NM_000393.5	P1
COL5A2	ENST00000618828.1	c.15+789C>T		intron_variant		5
COL5A2	ENST00000649966.1	c.507+789C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.864 AC: 130989 AN: 151572 Hom.: 57495 Cov.: 31

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.864 AC: 131046 AN: 151690 Hom.: 57508 Cov.: 31 AF XY: 0.863 AC XY: 64027 AN XY: 74150

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.950

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.848

Gnomad4 FIN AF: 0.959

Gnomad4 NFE AF: 0.954

Gnomad4 OTH AF: 0.870

Alfa AF: 0.899 Hom.: 14439

Bravo AF: 0.845

Asia WGS AF: 0.782 AC: 2713 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.030
Dann	Benign	0.14

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: rs10165260; hg19: chr2-189952632;