rs76511879

Positions:

chr2-189110349-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000393.5(COL5A2):c.198T>C(p.Asn66=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 1,614,164 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 41 hom. )

Consequence

COL5A2
NM_000393.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.924

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 2-189110349-A-G is Benign according to our data. Variant chr2-189110349-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 136961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.924 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00342 (521/152302) while in subpopulation SAS AF= 0.0151 (73/4828). AF 95% confidence interval is 0.0123. There are 2 homozygotes in gnomad4. There are 251 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 521 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
COL5A2	NM_000393.5 linkuse as main transcript	c.198T>C	p.Asn66=	synonymous_variant	2/54	ENST00000374866.9
COL5A2	XM_011510573.4 linkuse as main transcript	c.60T>C	p.Asn20=	synonymous_variant	5/57
COL5A2	XM_047443251.1 linkuse as main transcript	c.60T>C	p.Asn20=	synonymous_variant	7/59
COL5A2	XM_047443252.1 linkuse as main transcript	c.60T>C	p.Asn20=	synonymous_variant	6/58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
COL5A2	ENST00000374866.9 linkuse as main transcript	c.198T>C	p.Asn66=	synonymous_variant	2/54	1	NM_000393.5	P1
COL5A2	ENST00000649966.1 linkuse as main transcript	c.60T>C	p.Asn20=	synonymous_variant	2/11
COL5A2	ENST00000618828.1 linkuse as main transcript	c.-433T>C		5_prime_UTR_variant	2/47	5

Frequencies

GnomAD3 genomes

AF:

0.00343

AC:

522

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00512

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00531

AC:

1334

AN:

251350

Hom.:

AF XY:

0.00622

AC XY:

845

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00254

Gnomad ASJ exome

AF:

0.00764

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0165

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00527

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00520

AC:

7595

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

4020

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.00918

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0161

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.00486

Gnomad4 OTH exome

AF:

0.00560

GnomAD4 genome

AF:

0.00342

AC:

521

AN:

152302

Hom.:

Cov.:

AF XY:

0.00337

AC XY:

251

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0151

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00512

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00454

Hom.:

Bravo

AF:

0.00338

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00562

EpiControl

AF:

0.00599

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 08, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 21, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 28, 2013	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. -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Ehlers-Danlos syndrome, classic type, 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 08, 2023	- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 18, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Ehlers-Danlos syndrome type 7A

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Ehlers-Danlos syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 14, 2022

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Connective tissue disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Nov 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.8

DANN

Benign

0.74

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

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