2-189032668-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000393.5(COL5A2):c.*1402T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 152,420 control chromosomes in the GnomAD database, including 720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.095 (720 hom., cov: 32)
  • Exomes 𝑓: 0.087 (0 hom.)
• Consequence: COL5A2 NM_000393.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.00400

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-189032668-A-C is Benign according to our data. Variant chr2-189032668-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 333106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A2	NM_000393.5	c.*1402T>G		3_prime_UTR_variant	54/54	ENST00000374866.9
COL5A2	XM_011510573.4	c.*1402T>G		3_prime_UTR_variant	57/57
COL5A2	XM_047443251.1	c.*1402T>G		3_prime_UTR_variant	59/59
COL5A2	XM_047443252.1	c.*1402T>G		3_prime_UTR_variant	58/58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A2	ENST00000374866.9	c.*1402T>G		3_prime_UTR_variant	54/54	1	NM_000393.5	P1
COL5A2	ENST00000618828.1	c.*1402T>G		3_prime_UTR_variant	47/47	5

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14522 AN: 152046 Hom.: 720 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0866 AC: 22 AN: 254 Hom.: 0 Cov.: 0 AF XY: 0.0671 AC XY: 11 AN XY: 164

Gnomad4 FIN exome AF: 0.0887

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0955 AC: 14525 AN: 152166 Hom.: 720 Cov.: 32 AF XY: 0.0968 AC XY: 7203 AN XY: 74402

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.0982

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0892

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.105

Alfa AF: 0.108 Hom.: 1180

Bravo AF: 0.0937

Asia WGS AF: 0.124 AC: 429 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Ehlers-Danlos syndrome, classic type, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Ehlers-Danlos syndrome type 7A Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.1
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs11186; hg19: chr2-189897394;