rs139189200

Positions:

chr2-189061582-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2

The NM_000393.5(COL5A2):c.2011C>T(p.Pro671Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000748 in 1,613,340 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 7 hom. )

Consequence

COL5A2
NM_000393.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.28

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:

COL5A2 (HGNC:):

COL5A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), COL5A2. . Gene score misZ 2.4395 (greater than the threshold 3.09). Trascript score misZ 3.3523 (greater than threshold 3.09). GenCC has associacion of gene with Ehlers-Danlos syndrome, classic type, 2, Ehlers-Danlos syndrome, classic type.

BP4

Computational evidence support a benign effect (MetaRNN=0.01839903).

BP6

Variant 2-189061582-G-A is Benign according to our data. Variant chr2-189061582-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 180303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 191 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A2	NM_000393.5 linkuse as main transcript	c.2011C>T	p.Pro671Ser	missense_variant	30/54	ENST00000374866.9	NP_000384.2	P05997
COL5A2	XM_011510573.4 linkuse as main transcript	c.1873C>T	p.Pro625Ser	missense_variant	33/57		XP_011508875.1
COL5A2	XM_047443251.1 linkuse as main transcript	c.1873C>T	p.Pro625Ser	missense_variant	35/59		XP_047299207.1
COL5A2	XM_047443252.1 linkuse as main transcript	c.1873C>T	p.Pro625Ser	missense_variant	34/58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL5A2	ENST00000374866.9 linkuse as main transcript	c.2011C>T	p.Pro671Ser	missense_variant	30/54	1	NM_000393.5	ENSP00000364000.3	P05997
COL5A2	ENST00000618828.1 linkuse as main transcript	c.850C>T	p.Pro284Ser	missense_variant	23/47	5		ENSP00000482184.1	A0A087WYX9
COL5A2	ENST00000470524.2 linkuse as main transcript	n.117C>T		non_coding_transcript_exon_variant	3/8	5

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

191

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0154

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00156

AC:

391

AN:

251178

Hom.:

AF XY:

0.00159

AC XY:

216

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0134

Gnomad NFE exome

AF:

0.000775

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.000695

AC:

1015

AN:

1461166

Hom.:

Cov.:

AF XY:

0.000638

AC XY:

464

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0143

Gnomad4 NFE exome

AF:

0.000185

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.00126

AC:

191

AN:

152174

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0154

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000309

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00155

AC:

188

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Blueprint Genetics	Sep 17, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 10, 2024	This alteration is classified as likely 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, classic type, 2

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 13, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 22, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

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

Dec 03, 2023

- -

Ehlers-Danlos syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Nov 19, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 09, 2019

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.38

T;T;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;D;D

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Uncertain

0.52

MutationAssessor

Benign

1.9

L;.;L

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.8

N;.;.

REVEL

Uncertain

0.60

Sift

Benign

0.13

T;.;.

Sift4G

Benign

0.22

T;T;.

Polyphen

0.94

P;.;P

Vest4

0.32

MVP

0.65

MPC

0.64

ClinPred

0.066

GERP RS

5.0

Varity_R

0.11

gMVP

0.43

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