rs73978832

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000393.5(COL5A2):c.1006-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,608,904 control chromosomes in the GnomAD database, including 415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 24 hom., cov: 32)

Exomes 𝑓: 0.021 ( 391 hom. )

Consequence

COL5A2
NM_000393.5 intron

Scores

Splicing: ADA: 0.00002179

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.16

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-189078578-G-A is Benign according to our data. Variant chr2-189078578-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 136933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-189078578-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0154 (2348/152150) while in subpopulation NFE AF= 0.02 (1363/67996). AF 95% confidence interval is 0.0192. There are 24 homozygotes in gnomad4. There are 1156 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2348 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5 link	c.1006-9C>T	intron_variant	Intron 15 of 53	ENST00000374866.9	NP_000384.2	P05997
COL5A2	XM_011510573.4 link	c.868-9C>T	intron_variant	Intron 18 of 56		XP_011508875.1
COL5A2	XM_047443251.1 link	c.868-9C>T	intron_variant	Intron 20 of 58		XP_047299207.1
COL5A2	XM_047443252.1 link	c.868-9C>T	intron_variant	Intron 19 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9 link	c.1006-9C>T		intron_variant	Intron 15 of 53	1	NM_000393.5	ENSP00000364000.3		P05997
COL5A2	ENST00000618828.1 link	c.358+502C>T		intron_variant	Intron 15 of 46	5		ENSP00000482184.1		A0A087WYX9

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2351

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00396

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.0234

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.0324

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0201

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0171

AC:

4305

AN:

251310

Hom.:

AF XY:

0.0176

AC XY:

2396

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00412

Gnomad AMR exome

AF:

0.00999

Gnomad ASJ exome

AF:

0.0266

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0125

Gnomad FIN exome

AF:

0.0325

Gnomad NFE exome

AF:

0.0214

Gnomad OTH exome

AF:

0.0171

GnomAD4 exome

AF:

0.0206

AC:

30032

AN:

1456754

Hom.:

391

Cov.:

AF XY:

0.0205

AC XY:

14840

AN XY:

724970

show subpopulations

Gnomad4 AFR exome

AF:

0.00327

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0276

Gnomad4 EAS exome

AF:

0.00388

Gnomad4 SAS exome

AF:

0.0135

Gnomad4 FIN exome

AF:

0.0299

Gnomad4 NFE exome

AF:

0.0222

Gnomad4 OTH exome

AF:

0.0184

GnomAD4 genome

AF:

0.0154

AC:

2348

AN:

152150

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

1156

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00395

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.0234

Gnomad4 EAS

AF:

0.00271

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.0324

Gnomad4 NFE

AF:

0.0200

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0183

Hom.:

Bravo

AF:

0.0143

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Dec 11, 2012

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jul 21, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome, classic type, 2

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome type 7A

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome

Benign:1

Jul 16, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.8

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over