rs144344474

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_000393.5(COL5A2):c.975C>T(p.Pro325Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,612,866 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 16 hom. )

Consequence

COL5A2
NM_000393.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.395

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Ehlers-Danlos syndrome, classic type
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Ehlers-Danlos syndrome, classic type, 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp

COL5A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 2-189079093-G-A is Benign according to our data. Variant chr2-189079093-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.395 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00707 (1076/152178) while in subpopulation AFR AF = 0.0239 (993/41528). AF 95% confidence interval is 0.0227. There are 12 homozygotes in GnomAd4. There are 515 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1076 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000393.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	NM_000393.5	MANE Select	c.975C>T	p.Pro325Pro	synonymous	Exon 15 of 54	NP_000384.2	P05997

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL5A2	ENST00000374866.9	TSL:1 MANE Select	c.975C>T	p.Pro325Pro	synonymous	Exon 15 of 54	ENSP00000364000.3	P05997
COL5A2	ENST00000858728.1		c.972C>T	p.Pro324Pro	synonymous	Exon 15 of 54	ENSP00000528787.1
COL5A2	ENST00000858729.1		c.975C>T	p.Pro325Pro	synonymous	Exon 15 of 53	ENSP00000528788.1

Frequencies

GnomAD3 genomes

AF:

0.00705

AC:

1072

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00256

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00479

GnomAD2 exomes

AF:

0.00205

AC:

513

AN:

250826

AF XY:

0.00159

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.000842

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000397

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00104

AC:

1522

AN:

1460688

Hom.:

Cov.:

AF XY:

0.000995

AC XY:

723

AN XY:

726704

show subpopulations

African (AFR)

AF:

0.0269

AC:

897

AN:

33402

American (AMR)

AF:

0.00110

AC:

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.00146

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.000174

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00780

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000288

AC:

320

AN:

1111146

Other (OTH)

AF:

0.00262

AC:

158

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

135

202

270

337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00707

AC:

1076

AN:

152178

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

515

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0239

AC:

993

AN:

41528

American (AMR)

AF:

0.00255

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68014

Other (OTH)

AF:

0.00474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

142

190

237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00379

Hom.:

Bravo

AF:

0.00794

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000711

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Ehlers-Danlos syndrome, classic type, 2 (2)

not provided (2)

Ehlers-Danlos syndrome (1)

Ehlers-Danlos syndrome type 7A (1)

Ehlers-Danlos syndrome, classic type, 1 (1)

Familial thoracic aortic aneurysm and aortic dissection (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.8

(source)

DANN

Benign

0.56

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over