dbSNP rs766925699: COL5A2:p.Pro58Leu (chr2-189110374-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM2PP3_ModerateBS1

The NM_000393.5(COL5A2):c.173C>T(p.Pro58Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,856 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic 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: 0.0000027 ( 1 hom. )

Consequence

COL5A2
NM_000393.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.85

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.856

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00000274 (4/1461856) while in subpopulation SAS AF= 0.0000464 (4/86256). AF 95% confidence interval is 0.0000158. There are 1 homozygotes in gnomad4_exome. There are 3 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5 link	c.173C>T	p.Pro58Leu	missense_variant	Exon 2 of 54	ENST00000374866.9	NP_000384.2	P05997
COL5A2	XM_011510573.4 link	c.35C>T	p.Pro12Leu	missense_variant	Exon 5 of 57		XP_011508875.1
COL5A2	XM_047443251.1 link	c.35C>T	p.Pro12Leu	missense_variant	Exon 7 of 59		XP_047299207.1
COL5A2	XM_047443252.1 link	c.35C>T	p.Pro12Leu	missense_variant	Exon 6 of 58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL5A2	ENST00000374866.9 link	c.173C>T	p.Pro58Leu	missense_variant	Exon 2 of 54	1	NM_000393.5	ENSP00000364000.3	P05997
COL5A2	ENST00000649966.1 link	c.35C>T	p.Pro12Leu	missense_variant	Exon 2 of 11			ENSP00000496785.1	A0A3B3IRH9
COL5A2	ENST00000618828.1 link	c.-458C>T		5_prime_UTR_variant	Exon 2 of 47	5		ENSP00000482184.1	A0A087WYX9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251380

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135846

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:

0.00000274

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727228

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:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.96

.;D;D

M_CAP

Uncertain

0.085

MetaRNN

Pathogenic

0.86

D;D;D

MetaSVM

Uncertain

0.073

MutationAssessor

Pathogenic

3.0

M;M;.

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.8

D;.;.

REVEL

Uncertain

0.44

Sift

Uncertain

0.0060

D;.;.

Sift4G

Uncertain

0.0080

D;.;.

Polyphen

0.95

P;P;.

Vest4

0.55

MutPred

0.82

Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);.;

MVP

0.53

MPC

0.75

ClinPred

0.86

GERP RS

4.5

Varity_R

0.24

gMVP

0.77

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