2-189058904-ATTTT-ATTT

Variant names:

• chr2-189058904-AT-A
• rs5837121
• NM_000393.5:c.2086-12delA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000374866.9(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 ENST00000374866.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.50
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 213077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374866.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	NM_000393.5	MANE Select	c.2086-12delA		intron	N/A	NP_000384.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	ENST00000374866.9	TSL:1 MANE Select	c.2086-12delA		intron	N/A	ENSP00000364000.3
	COL5A2	ENST00000618828.1	TSL:5	c.925-12delA		intron	N/A	ENSP00000482184.1
	COL5A2	ENST00000470524.2	TSL:5	n.192-12delA		intron	N/A

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

GnomAD2 exomes AF: 0.680 AC: 106019 AN: 155846 AF XY: 0.680

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 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

African (AFR) AF: 0.563 AC: 15477 AN: 27502

American (AMR) AF: 0.559 AC: 21032 AN: 37642

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 12783 AN: 20074

East Asian (EAS) AF: 0.578 AC: 19045 AN: 32958

South Asian (SAS) AF: 0.588 AC: 40979 AN: 69662

European-Finnish (FIN) AF: 0.741 AC: 32549 AN: 43918

Middle Eastern (MID) AF: 0.725 AC: 3526 AN: 4864

European-Non Finnish (NFE) AF: 0.679 AC: 552915 AN: 813960

Other (OTH) AF: 0.647 AC: 29769 AN: 46044

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

African (AFR) AF: 0.727 AC: 29703 AN: 40884

American (AMR) AF: 0.818 AC: 12284 AN: 15012

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 3236 AN: 3432

East Asian (EAS) AF: 0.811 AC: 4140 AN: 5104

South Asian (SAS) AF: 0.842 AC: 3993 AN: 4740

European-Finnish (FIN) AF: 0.943 AC: 9356 AN: 9918

Middle Eastern (MID) AF: 0.876 AC: 254 AN: 290

European-Non Finnish (NFE) AF: 0.948 AC: 63792 AN: 67296

Other (OTH) AF: 0.864 AC: 1787 AN: 2068

Alfa AF: 0.702 Hom.: 2945

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Ehlers-Danlos syndrome, classic type, 1 (1)
-	-	1	Ehlers-Danlos syndrome, classic type, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5837121; hg19: chr2-189923630;