rs142388534

Variant names:

• chr2-189110298-G-A
• rs142388534
• NM_000393.5:c.249C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-189110298-G-A
• chr2-189110298-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000393.5(COL5A2):​c.249C>T​(p.Ala83Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,614,060 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0062 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (13 hom.)
• Consequence: COL5A2 NM_000393.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.34

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 2-189110298-G-A is Benign according to our data. Variant chr2-189110298-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 136962.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 = 0.00622 (946/152194) while in subpopulation AFR AF= 0.0211 (876/41512). AF 95% confidence interval is 0.0199. There are 9 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 946 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.249C>T	p.Ala83Ala	synonymous_variant	Exon 2 of 54	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.111C>T	p.Ala37Ala	synonymous_variant	Exon 5 of 57		XP_011508875.1
COL5A2	XM_047443251.1	c.111C>T	p.Ala37Ala	synonymous_variant	Exon 7 of 59		XP_047299207.1
COL5A2	XM_047443252.1	c.111C>T	p.Ala37Ala	synonymous_variant	Exon 6 of 58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.249C>T	p.Ala83Ala	synonymous_variant	Exon 2 of 54	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.-382C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 47	5		ENSP00000482184.1
COL5A2	ENST00000649966.1	c.111C>T	p.Ala37Ala	synonymous_variant	Exon 2 of 11			ENSP00000496785.1
COL5A2	ENST00000618828.1	c.-382C>T		5_prime_UTR_variant	Exon 2 of 47	5		ENSP00000482184.1

Frequencies

GnomAD3 genomes AF: 0.00621 AC: 945 AN: 152076 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00185 AC: 464 AN: 251254 Hom.: 4 AF XY: 0.00147 AC XY: 199 AN XY: 135786

Gnomad AFR exome AF: 0.0219

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00367

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.000835 AC: 1221 AN: 1461866 Hom.: 13 Cov.: 33 AF XY: 0.000787 AC XY: 572 AN XY: 727236

Gnomad4 AFR exome AF: 0.0235

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00375

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000119

Gnomad4 OTH exome AF: 0.00210

GnomAD4 genome AF: 0.00622 AC: 946 AN: 152194 Hom.: 9 Cov.: 32 AF XY: 0.00578 AC XY: 430 AN XY: 74402

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00392 Hom.: 3

Bravo AF: 0.00703

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Jul 21, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 21, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Sep 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Aug 25, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.1
DANN	Benign	0.80

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: rs142388534; hg19: chr2-189975024;