ENST00000747641.1:n.285-31805C>T

Variant names:

• chr2-189390032-G-A
• rs1112578
• ENST00000747641.1:n.285-31805C>T

Variant summary

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

The ENST00000747641.1(ENSG00000288866):​n.285-31805C>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: ENSG00000288866 ENST00000747641.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 3 publications found

Genes affected

ENSG00000288866 (HGNC:):

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=-0.77).
• 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 rank	MANE	Protein	UniProt
COL5A2	XM_011510573.4	c.-331+39260C>T		intron_variant	Intron 2 of 56		XP_011508875.1
COL5A2	XM_047443251.1	c.-502-391C>T		intron_variant	Intron 2 of 58		XP_047299207.1
COL5A2	XM_047443252.1	c.-455-41836C>T		intron_variant	Intron 1 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000288866	ENST00000747641.1	n.285-31805C>T		intron_variant	Intron 2 of 7
ENSG00000288866	ENST00000747642.1	n.213+20409C>T		intron_variant	Intron 2 of 4
ENSG00000288866	ENST00000747643.1	n.348-31805C>T		intron_variant	Intron 2 of 4

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

African (AFR) AF: 0.316 AC: 13071 AN: 41374

American (AMR) AF: 0.597 AC: 9093 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2279 AN: 3468

East Asian (EAS) AF: 0.690 AC: 3567 AN: 5168

South Asian (SAS) AF: 0.591 AC: 2846 AN: 4812

European-Finnish (FIN) AF: 0.652 AC: 6881 AN: 10548

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46008 AN: 67950

Other (OTH) AF: 0.593 AC: 1251 AN: 2108

Alfa AF: 0.643 Hom.: 22982

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
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs1112578; hg19: chr2-190254758;