Variant 2-189057323-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_000393.5(COL5A2):c.2334C>A(p.Asp778Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.000023 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00055 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COL5A2
NM_000393.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.768

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 Likely_benign. Variant got -1 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=0.25471544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A2	NM_000393.5 linkuse as main transcript	c.2334C>A	p.Asp778Glu	missense_variant	34/54	ENST00000374866.9	NP_000384.2	P05997
COL5A2	XM_011510573.4 linkuse as main transcript	c.2196C>A	p.Asp732Glu	missense_variant	37/57		XP_011508875.1
COL5A2	XM_047443251.1 linkuse as main transcript	c.2196C>A	p.Asp732Glu	missense_variant	39/59		XP_047299207.1
COL5A2	XM_047443252.1 linkuse as main transcript	c.2196C>A	p.Asp732Glu	missense_variant	38/58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL5A2	ENST00000374866.9 linkuse as main transcript	c.2334C>A	p.Asp778Glu	missense_variant	34/54	1	NM_000393.5	ENSP00000364000.3	P05997
COL5A2	ENST00000618828.1 linkuse as main transcript	c.1173C>A	p.Asp391Glu	missense_variant	27/47	5		ENSP00000482184.1	A0A087WYX9
COL5A2	ENST00000470524.2 linkuse as main transcript	n.440C>A		non_coding_transcript_exon_variant	7/8	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

132972

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000465

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000547

AC:

518

AN:

946484

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

261

AN XY:

488062

show subpopulations

Gnomad4 AFR exome

AF:

0.000171

Gnomad4 AMR exome

AF:

0.0000234

Gnomad4 ASJ exome

AF:

0.0000934

Gnomad4 EAS exome

AF:

0.0000594

Gnomad4 SAS exome

AF:

0.000118

Gnomad4 FIN exome

AF:

0.0000421

Gnomad4 NFE exome

AF:

0.000734

Gnomad4 OTH exome

AF:

0.000408

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000226

AC:

AN:

132980

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

63206

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000466

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000157

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.14

T;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.071

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.86

.;D;T

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

-0.060

N;.;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.22

N;.;.

REVEL

Benign

0.29

Sift

Benign

0.81

T;.;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.36

B;.;B

Vest4

0.29

MutPred

0.25

Loss of methylation at R779 (P = 0.1796);.;Loss of methylation at R779 (P = 0.1796);

MVP

0.60

MPC

0.24

ClinPred

0.86

GERP RS

5.0

Varity_R

0.053

gMVP

0.17

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over