2-189058904-A-AT

Position:

• chr2-189058904-A-AT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000393.5(COL5A2):​c.2086-12dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (52 hom., cov: 0)
  • Exomes 𝑓: 0.012 (13 hom.)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.50

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-189058904-A-AT is Benign according to our data. Variant chr2-189058904-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 377039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.2086-12dupA		intron_variant		ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.1948-12dupA		intron_variant			XP_011508875.1
COL5A2	XM_047443251.1	c.1948-12dupA		intron_variant			XP_047299207.1
COL5A2	XM_047443252.1	c.1948-12dupA		intron_variant			XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.2086-12dupA		intron_variant		1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.925-12dupA		intron_variant		5		ENSP00000482184.1
COL5A2	ENST00000470524.2	n.192-12dupA		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2339 AN: 149566 Hom.: 49 Cov.: 0

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.00233

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.00948

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.0122

GnomAD4 exome AF: 0.0121 AC: 13216 AN: 1095856 Hom.: 13 Cov.: 0 AF XY: 0.0142 AC XY: 7790 AN XY: 549288

Gnomad4 AFR exome AF: 0.0300

Gnomad4 AMR exome AF: 0.0424

Gnomad4 ASJ exome AF: 0.00374

Gnomad4 EAS exome AF: 0.0748

Gnomad4 SAS exome AF: 0.0871

Gnomad4 FIN exome AF: 0.0108

Gnomad4 NFE exome AF: 0.00113

Gnomad4 OTH exome AF: 0.0167

GnomAD4 genome AF: 0.0157 AC: 2352 AN: 149674 Hom.: 52 Cov.: 0 AF XY: 0.0172 AC XY: 1257 AN XY: 73028

Gnomad4 AFR AF: 0.0234

Gnomad4 AMR AF: 0.0323

Gnomad4 ASJ AF: 0.00233

Gnomad4 EAS AF: 0.0576

Gnomad4 SAS AF: 0.0859

Gnomad4 FIN AF: 0.00948

Gnomad4 NFE AF: 0.00110

Gnomad4 OTH AF: 0.0135

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Oct 13, 2016

- -

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs5837121; hg19: chr2-189923630;