Variant rs200703515 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_000393.5(COL5A2):c.4471G>T(p.Val1491Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.8e-7 ( 0 hom. )

Consequence

COL5A2
NM_000393.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.73

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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=0.11244866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COL5A2	NM_000393.5 linkuse as main transcript	c.4471G>T	p.Val1491Phe	missense_variant	54/54	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4 linkuse as main transcript	c.4333G>T	p.Val1445Phe	missense_variant	57/57		XP_011508875.1
COL5A2	XM_047443251.1 linkuse as main transcript	c.4333G>T	p.Val1445Phe	missense_variant	59/59		XP_047299207.1
COL5A2	XM_047443252.1 linkuse as main transcript	c.4333G>T	p.Val1445Phe	missense_variant	58/58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9 linkuse as main transcript	c.4471G>T	p.Val1491Phe	missense_variant	54/54	1	NM_000393.5	ENSP00000364000	P1
COL5A2	ENST00000618828.1 linkuse as main transcript	c.3310G>T	p.Val1104Phe	missense_variant	47/47	5		ENSP00000482184

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727170

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:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.0040

DANN

Benign

0.83

DEOGEN2

Uncertain

0.64

D;T;D

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.81

.;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.12

N;.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.3

N;.;.

REVEL

Benign

0.20

Sift

Benign

0.076

T;.;.

Sift4G

Benign

0.55

T;T;.

Polyphen

0.0

B;.;B

Vest4

0.32

MutPred

0.57

Loss of sheet (P = 0.1398);.;Loss of sheet (P = 0.1398);

MVP

0.46

MPC

0.34

ClinPred

0.16

GERP RS

-10

Varity_R

0.12

gMVP

0.71

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over