Variant 2-189110428-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4BS1BS2

The NM_000393.5(COL5A2):c.119C>A(p.Ala40Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

COL5A2
NM_000393.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.61

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28366753).

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00000547 (8/1461432) while in subpopulation SAS AF= 0.0000928 (8/86244). AF 95% confidence interval is 0.0000458. There are 0 homozygotes in gnomad4_exome. There are 6 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A2	NM_000393.5 link	c.119C>A	p.Ala40Asp	missense_variant	2/54	ENST00000374866.9	NP_000384.2	P05997
COL5A2	XM_011510573.4 link	c.-20C>A		5_prime_UTR_variant	5/57		XP_011508875.1
COL5A2	XM_047443251.1 link	c.-20C>A		5_prime_UTR_variant	7/59		XP_047299207.1
COL5A2	XM_047443252.1 link	c.-20C>A		5_prime_UTR_variant	6/58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL5A2	ENST00000374866.9 link	c.119C>A	p.Ala40Asp	missense_variant	2/54	1	NM_000393.5	ENSP00000364000.3	P05997
COL5A2	ENST00000618828.1 link	c.-512C>A		5_prime_UTR_variant	2/47	5		ENSP00000482184.1	A0A087WYX9
COL5A2	ENST00000649966.1 link	c.-20C>A		5_prime_UTR_variant	2/11			ENSP00000496785.1	A0A3B3IRH9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251200

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135780

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461432

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727068

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:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.027

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.65

.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.77

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.30

N;.

REVEL

Benign

0.13

Sift

Benign

0.16

T;.

Sift4G

Uncertain

0.054

T;.

Polyphen

0.0010

B;B

Vest4

0.26

MutPred

0.56

Gain of disorder (P = 0.0326);Gain of disorder (P = 0.0326);

MVP

0.17

MPC

1.0

ClinPred

0.49

GERP RS

5.4

Varity_R

0.15

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over