2-189133613-C-T

Variant names:

• chr2-189133613-C-T
• rs6752781
• NM_000393.5:c.98-23164G>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.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
• 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 = 0.909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000393.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	NM_000393.5	MANE Select	c.98-23164G>A		intron	N/A	NP_000384.2	P05997

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	ENST00000374866.9	TSL:1 MANE Select	c.98-23164G>A		intron	N/A	ENSP00000364000.3	P05997
	COL5A2	ENST00000858728.1		c.98-23167G>A		intron	N/A	ENSP00000528787.1
	COL5A2	ENST00000858729.1		c.98-23164G>A		intron	N/A	ENSP00000528788.1

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

African (AFR) AF: 0.498 AC: 20612 AN: 41392

American (AMR) AF: 0.829 AC: 12667 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3178 AN: 3472

East Asian (EAS) AF: 0.843 AC: 4330 AN: 5134

South Asian (SAS) AF: 0.914 AC: 4404 AN: 4820

European-Finnish (FIN) AF: 0.941 AC: 9976 AN: 10606

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62193 AN: 67996

Other (OTH) AF: 0.807 AC: 1705 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.90
DANN	Benign	0.49
PhyloP100		0.091
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: rs6752781; hg19: chr2-189998339;