2-189058904-AT-A

Position:

• chr2-189058904-AT-A

Variant summary

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

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

• Frequency:
  • Genomes: 𝑓 0.86 (56588 hom., cov: 0)
  • Exomes 𝑓: 0.66 (183773 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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-AT-A is Benign according to our data. Variant chr2-189058904-AT-A is described in ClinVar as [Benign]. Clinvar id is 213077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-189058904-AT-A is described in Lovd as [Benign]. Variant chr2-189058904-AT-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.865 AC: 129354 AN: 149544 Hom.: 56567 Cov.: 0

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.881

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.865

GnomAD3 exomes AF: 0.680 AC: 106019 AN: 155846 Hom.: 29296 AF XY: 0.680 AC XY: 56394 AN XY: 82898

Gnomad AFR exome AF: 0.608

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.649

Gnomad EAS exome AF: 0.611

Gnomad SAS exome AF: 0.593

Gnomad FIN exome AF: 0.861

Gnomad NFE exome AF: 0.736

Gnomad OTH exome AF: 0.657

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.664 AC: 728075 AN: 1096624 Hom.: 183773 Cov.: 0 AF XY: 0.661 AC XY: 363541 AN XY: 549710

Gnomad4 AFR exome AF: 0.563

Gnomad4 AMR exome AF: 0.559

Gnomad4 ASJ exome AF: 0.637

Gnomad4 EAS exome AF: 0.578

Gnomad4 SAS exome AF: 0.588

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.647

GnomAD4 genome AF: 0.865 AC: 129422 AN: 149650 Hom.: 56588 Cov.: 0 AF XY: 0.864 AC XY: 63090 AN XY: 73020

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.948

Gnomad4 OTH AF: 0.864

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant was found in TAADV2-WO-FBN1-PANCARD,TAADV2-PANCARD,TAAD,TAADV2-1 -

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 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;