NM_000393.5:c.799-426A>G

Variant names:

• chr2-189084463-T-C
• rs6434322
• NM_000393.5:c.799-426A>G

Variant summary

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

The NM_000393.5(COL5A2):​c.799-426A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,200 control chromosomes in the GnomAD database, including 58,741 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 0.87 (58741 hom., cov: 33)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• 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=-0.95).
• 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 rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.799-426A>G		intron_variant	Intron 11 of 53	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.661-426A>G		intron_variant	Intron 14 of 56		XP_011508875.1
COL5A2	XM_047443251.1	c.661-426A>G		intron_variant	Intron 16 of 58		XP_047299207.1
COL5A2	XM_047443252.1	c.661-426A>G		intron_variant	Intron 15 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.799-426A>G		intron_variant	Intron 11 of 53	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.169-426A>G		intron_variant	Intron 11 of 46	5		ENSP00000482184.1

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132838 AN: 152084 Hom.: 58720 Cov.: 33

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.876

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

GnomAD4 genome AF: 0.873 AC: 132908 AN: 152200 Hom.: 58741 Cov.: 33 AF XY: 0.873 AC XY: 64956 AN XY: 74420

African (AFR) AF: 0.738 AC: 30647 AN: 41516

American (AMR) AF: 0.824 AC: 12598 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3299 AN: 3472

East Asian (EAS) AF: 0.815 AC: 4216 AN: 5172

South Asian (SAS) AF: 0.848 AC: 4094 AN: 4826

European-Finnish (FIN) AF: 0.959 AC: 10180 AN: 10610

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64889 AN: 68004

Other (OTH) AF: 0.875 AC: 1842 AN: 2106

Alfa AF: 0.879 Hom.: 20223

Bravo AF: 0.855

Asia WGS AF: 0.786 AC: 2729 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	3.0
DANN	Benign	0.71
PhyloP100		-0.69
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: rs6434322; hg19: chr2-189949189;