Variant 2-189057349-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The ENST00000374866.9(COL5A2):c.2308G>T(p.Ala770Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,458,208 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. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A770A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

COL5A2
ENST00000374866.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81

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 2 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=0.34439376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COL5A2	NM_000393.5 linkuse as main transcript	c.2308G>T	p.Ala770Ser	missense_variant	34/54	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4 linkuse as main transcript	c.2170G>T	p.Ala724Ser	missense_variant	37/57		XP_011508875.1
COL5A2	XM_047443251.1 linkuse as main transcript	c.2170G>T	p.Ala724Ser	missense_variant	39/59		XP_047299207.1
COL5A2	XM_047443252.1 linkuse as main transcript	c.2170G>T	p.Ala724Ser	missense_variant	38/58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
COL5A2	ENST00000374866.9 linkuse as main transcript	c.2308G>T	p.Ala770Ser	missense_variant	34/54	1	NM_000393.5	ENSP00000364000	P1
COL5A2	ENST00000618828.1 linkuse as main transcript	c.1147G>T	p.Ala383Ser	missense_variant	27/47	5		ENSP00000482184
COL5A2	ENST00000470524.2 linkuse as main transcript	n.414G>T		non_coding_transcript_exon_variant	7/8	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251104

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135730

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:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458208

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725542

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Connective tissue disorder

Uncertain:1

Uncertain significance, 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

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

0.0056

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;T;T

Eigen

Benign

-0.0072

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.86

.;D;D

M_CAP

Benign

0.082

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Uncertain

0.078

MutationAssessor

Benign

0.69

N;.;N

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.90

N;.;.

REVEL

Uncertain

0.40

Sift

Benign

0.14

T;.;.

Sift4G

Benign

0.45

T;T;.

Polyphen

0.023

B;.;B

Vest4

0.23

MutPred

0.25

Gain of glycosylation at A770 (P = 0.0062);.;Gain of glycosylation at A770 (P = 0.0062);

MVP

0.40

MPC

0.24

ClinPred

0.36

GERP RS

5.9

Varity_R

0.087

gMVP

0.079

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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