2-189075378-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000393.5(COL5A2):c.1104+15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,566,624 control chromosomes in the GnomAD database, including 29 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 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 16 hom. )

Consequence

COL5A2
NM_000393.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.266

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-189075378-A-G is Benign according to our data. Variant chr2-189075378-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00709 (1079/152280) while in subpopulation AFR AF = 0.024 (997/41572). AF 95% confidence interval is 0.0227. There are 13 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 1079 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.1104+15T>C		intron	N/A	NP_000384.2	P05997

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL5A2	ENST00000374866.9	TSL:1 MANE Select	c.1104+15T>C	intron	N/A	ENSP00000364000.3	P05997
COL5A2	ENST00000858728.1		c.1101+15T>C	intron	N/A	ENSP00000528787.1
COL5A2	ENST00000858729.1		c.1104+15T>C	intron	N/A	ENSP00000528788.1

Frequencies

GnomAD3 genomes

AF:

0.00706

AC:

1075

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

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:

0.00478

GnomAD2 exomes

AF:

0.00204

AC:

512

AN:

250610

AF XY:

0.00159

show subpopulations

Gnomad AFR exome

AF:

0.0247

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:

0.000388

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.00102

AC:

1443

AN:

1414344

Hom.:

Cov.:

AF XY:

0.000981

AC XY:

693

AN XY:

706502

show subpopulations

African (AFR)

AF:

0.0262

AC:

850

AN:

32424

American (AMR)

AF:

0.00110

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.00148

AC:

AN:

25756

East Asian (EAS)

AF:

0.00

AC:

AN:

39314

South Asian (SAS)

AF:

0.000177

AC:

AN:

84874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53212

Middle Eastern (MID)

AF:

0.00777

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.000280

AC:

300

AN:

1069766

Other (OTH)

AF:

0.00250

AC:

147

AN:

58742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

124

187

249

311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00709

AC:

1079

AN:

152280

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

515

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0240

AC:

997

AN:

41572

American (AMR)

AF:

0.00249

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68014

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

108

162

216

270

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:

0.00413

Hom.:

Bravo

AF:

0.00795

Asia WGS

AF:

0.00347

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

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

not provided (2)

Ehlers-Danlos syndrome type 7A (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.0

(source)

DANN

Benign

0.88

PhyloP100

-0.27

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

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