2-189040671-C-T

Variant names:

• chr2-189040671-C-T
• rs3923384
• NM_000393.5:c.3633+915G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000393.5(COL5A2):​c.3633+915G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,090 control chromosomes in the GnomAD database, including 57,801 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 (57801 hom., cov: 31)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.792
• Publications: 4 publications found

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]

COL5A2 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome, classic type

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Ehlers-Danlos syndrome, classic type, 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• 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 rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.3633+915G>A		intron_variant	Intron 50 of 53	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.3495+915G>A		intron_variant	Intron 53 of 56		XP_011508875.1
COL5A2	XM_047443251.1	c.3495+915G>A		intron_variant	Intron 55 of 58		XP_047299207.1
COL5A2	XM_047443252.1	c.3495+915G>A		intron_variant	Intron 54 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.3633+915G>A		intron_variant	Intron 50 of 53	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.2472+915G>A		intron_variant	Intron 43 of 46	5		ENSP00000482184.1

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131478 AN: 151972 Hom.: 57779 Cov.: 31

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.886

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: 0.865 AC: 131550 AN: 152090 Hom.: 57801 Cov.: 31 AF XY: 0.865 AC XY: 64317 AN XY: 74350

African (AFR) AF: 0.702 AC: 29100 AN: 41430

American (AMR) AF: 0.831 AC: 12690 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3305 AN: 3472

East Asian (EAS) AF: 0.833 AC: 4290 AN: 5150

South Asian (SAS) AF: 0.853 AC: 4110 AN: 4820

European-Finnish (FIN) AF: 0.959 AC: 10179 AN: 10610

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64899 AN: 68016

Other (OTH) AF: 0.870 AC: 1835 AN: 2110

Alfa AF: 0.890 Hom.: 7950

Bravo AF: 0.846

Asia WGS AF: 0.796 AC: 2772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.0
DANN	Benign	0.61
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3923384; hg19: chr2-189905397;