2-189032905-C-T

Variant names:

• chr2-189032905-C-T
• rs13914
• NM_000393.5:c.*1165G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000393.5(COL5A2):​c.*1165G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 152,508 control chromosomes in the GnomAD database, including 201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (201 hom., cov: 32)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: COL5A2 NM_000393.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.55
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-189032905-C-T is Benign according to our data. Variant chr2-189032905-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 333109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0816 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000393.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	NM_000393.5	MANE Select	c.*1165G>A		3_prime_UTR	Exon 54 of 54	NP_000384.2	P05997

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	ENST00000374866.9	TSL:1 MANE Select	c.*1165G>A		3_prime_UTR	Exon 54 of 54	ENSP00000364000.3	P05997
	COL5A2	ENST00000618828.1	TSL:5	c.*1165G>A		3_prime_UTR	Exon 47 of 47	ENSP00000482184.1	A0A087WYX9

Frequencies

GnomAD3 genomes AF: 0.0466 AC: 7083 AN: 151956 Hom.: 203 Cov.: 32

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0437

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.0451

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0468

GnomAD4 exome AF: 0.0208 AC: 9 AN: 432 Hom.: 0 Cov.: 0 AF XY: 0.0269 AC XY: 7 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0188 AC: 8 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.0466 AC: 7086 AN: 152076 Hom.: 201 Cov.: 32 AF XY: 0.0469 AC XY: 3491 AN XY: 74356

African (AFR) AF: 0.0839 AC: 3482 AN: 41508

American (AMR) AF: 0.0434 AC: 662 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 72 AN: 3466

East Asian (EAS) AF: 0.0739 AC: 383 AN: 5180

South Asian (SAS) AF: 0.0441 AC: 212 AN: 4812

European-Finnish (FIN) AF: 0.0304 AC: 322 AN: 10594

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0265 AC: 1800 AN: 67936

Other (OTH) AF: 0.0478 AC: 101 AN: 2114

Alfa AF: 0.0339 Hom.: 318

Bravo AF: 0.0498

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Ehlers-Danlos syndrome type 7A (1)
-	-	1	Ehlers-Danlos syndrome, classic type, 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.19
PhyloP100		-1.6
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: rs13914; hg19: chr2-189897631; COSMIC: COSV66411433;