rs7420331

Variant names:

• chr2-189095603-A-G
• rs7420331
• NM_000393.5:c.456+1674T>C

Variant summary

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

The NM_000393.5(COL5A2):​c.456+1674T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,026 control chromosomes in the GnomAD database, including 1,365 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 0.13 (1365 hom., cov: 30)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 3 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

ENSG00000228073 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.456+1674T>C		intron_variant	Intron 6 of 53	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.318+1674T>C		intron_variant	Intron 9 of 56		XP_011508875.1
COL5A2	XM_047443251.1	c.318+1674T>C		intron_variant	Intron 11 of 58		XP_047299207.1
COL5A2	XM_047443252.1	c.318+1674T>C		intron_variant	Intron 10 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.456+1674T>C		intron_variant	Intron 6 of 53	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.-175+1674T>C		intron_variant	Intron 6 of 46	5		ENSP00000482184.1
COL5A2	ENST00000649966.1	c.318+1674T>C		intron_variant	Intron 6 of 10			ENSP00000496785.1
ENSG00000228073	ENST00000419029.1	n.75-233A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20188 AN: 151908 Hom.: 1368 Cov.: 30

Gnomad AFR AF: 0.0987

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0970

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.133 AC: 20181 AN: 152026 Hom.: 1365 Cov.: 30 AF XY: 0.134 AC XY: 9959 AN XY: 74346

African (AFR) AF: 0.0986 AC: 4088 AN: 41460

American (AMR) AF: 0.132 AC: 2019 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3466

East Asian (EAS) AF: 0.0964 AC: 499 AN: 5176

South Asian (SAS) AF: 0.185 AC: 890 AN: 4812

European-Finnish (FIN) AF: 0.137 AC: 1453 AN: 10576

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9907 AN: 67954

Other (OTH) AF: 0.155 AC: 326 AN: 2108

Alfa AF: 0.138 Hom.: 719

Bravo AF: 0.129

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-1.4
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: rs7420331; hg19: chr2-189960329;