rs1112578

Positions:

• chr2-189390032-G-A
• chr2-189390032-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011510573.4(COL5A2):​c.-331+39260C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,856 control chromosomes in the GnomAD database, including 26,077 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 0.57 (26077 hom., cov: 31)
• Consequence: COL5A2 XM_011510573.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A2	XM_011510573.4	c.-331+39260C>T		intron_variant			XP_011508875.1
COL5A2	XM_047443251.1	c.-502-391C>T		intron_variant			XP_047299207.1
COL5A2	XM_047443252.1	c.-455-41836C>T		intron_variant			XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85837 AN: 151738 Hom.: 26064 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.566 AC: 85888 AN: 151856 Hom.: 26077 Cov.: 31 AF XY: 0.566 AC XY: 41983 AN XY: 74206

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.593

Alfa AF: 0.645 Hom.: 17011

Bravo AF: 0.549

Asia WGS AF: 0.600 AC: 2087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1112578; hg19: chr2-190254758;