2-189116486-G-T

Variant names:

• chr2-189116486-G-T
• rs13024858
• NM_000393.5:c.98-6037C>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.98-6037C>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
• Publications: 5 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=-0.96).
• 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 rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.98-6037C>A		intron_variant	Intron 1 of 53	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.-41-6037C>A		intron_variant	Intron 4 of 56		XP_011508875.1
COL5A2	XM_047443251.1	c.-41-6037C>A		intron_variant	Intron 6 of 58		XP_047299207.1
COL5A2	XM_047443252.1	c.-41-6037C>A		intron_variant	Intron 5 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.98-6037C>A		intron_variant	Intron 1 of 53	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.-533-6037C>A		intron_variant	Intron 1 of 46	5		ENSP00000482184.1
COL5A2	ENST00000649966.1	c.-41-6037C>A		intron_variant	Intron 1 of 10			ENSP00000496785.1

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

African (AFR) AF: 0.412 AC: 17063 AN: 41406

American (AMR) AF: 0.809 AC: 12362 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 3110 AN: 3472

East Asian (EAS) AF: 0.843 AC: 4364 AN: 5174

South Asian (SAS) AF: 0.912 AC: 4392 AN: 4814

European-Finnish (FIN) AF: 0.940 AC: 9964 AN: 10604

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.912 AC: 62040 AN: 68018

Other (OTH) AF: 0.775 AC: 1636 AN: 2112

Alfa AF: 0.869 Hom.: 97124

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
PhyloP100		-0.81
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: rs13024858; hg19: chr2-189981212;