2-189116486-G-T

Position:

• chr2-189116486-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.98-6037C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,086 control chromosomes in the GnomAD database, including 48,009 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 0.76 (48009 hom., cov: 32)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A2	NM_000393.5	c.98-6037C>A		intron_variant		ENST00000374866.9
COL5A2	XM_011510573.4	c.-41-6037C>A		intron_variant
COL5A2	XM_047443251.1	c.-41-6037C>A		intron_variant
COL5A2	XM_047443252.1	c.-41-6037C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A2	ENST00000374866.9	c.98-6037C>A		intron_variant		1	NM_000393.5	P1
COL5A2	ENST00000618828.1	c.-533-6037C>A		intron_variant		5
COL5A2	ENST00000649966.1	c.-41-6037C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116044 AN: 151966 Hom.: 48004 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.763 AC: 116076 AN: 152086 Hom.: 48009 Cov.: 32 AF XY: 0.767 AC XY: 57018 AN XY: 74350

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.912

Gnomad4 FIN AF: 0.940

Gnomad4 NFE AF: 0.912

Gnomad4 OTH AF: 0.775

Alfa AF: 0.886 Hom.: 79007

Bravo AF: 0.734

Asia WGS AF: 0.818 AC: 2846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.50

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: rs13024858; hg19: chr2-189981212;