chr2-189088782-C-T

Variant names:

• chr2-189088782-C-T
• rs58106884
• NM_000393.5:c.568-10G>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.568-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,608,852 control chromosomes in the GnomAD database, including 17,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1373 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15865 hom.)
• Consequence: COL5A2 NM_000393.5 intron
• Scores: Splicing: ADA: 0.001508
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.99
• Publications: 5 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=-0.61).
• BP6: Variant 2-189088782-C-T is Benign according to our data. Variant chr2-189088782-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 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.568-10G>A		intron	N/A	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.568-10G>A		intron	N/A	ENSP00000364000.3	P05997
	COL5A2	ENST00000858728.1		c.565-10G>A		intron	N/A	ENSP00000528787.1
	COL5A2	ENST00000858729.1		c.568-10G>A		intron	N/A	ENSP00000528788.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20211 AN: 151934 Hom.: 1376 Cov.: 33

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0985

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.141 AC: 35411 AN: 251338 AF XY: 0.147

Gnomad AFR exome AF: 0.0942

Gnomad AMR exome AF: 0.0948

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.0961

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.149

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.143 AC: 208752 AN: 1456800 Hom.: 15865 Cov.: 31 AF XY: 0.146 AC XY: 105694 AN XY: 725002

African (AFR) AF: 0.0928 AC: 3101 AN: 33410

American (AMR) AF: 0.102 AC: 4570 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5897 AN: 26088

East Asian (EAS) AF: 0.111 AC: 4405 AN: 39656

South Asian (SAS) AF: 0.188 AC: 16180 AN: 86098

European-Finnish (FIN) AF: 0.142 AC: 7561 AN: 53410

Middle Eastern (MID) AF: 0.244 AC: 1400 AN: 5744

European-Non Finnish (NFE) AF: 0.141 AC: 156665 AN: 1107446

Other (OTH) AF: 0.149 AC: 8973 AN: 60228

GnomAD4 genome AF: 0.133 AC: 20204 AN: 152052 Hom.: 1373 Cov.: 33 AF XY: 0.134 AC XY: 9970 AN XY: 74332

African (AFR) AF: 0.0983 AC: 4078 AN: 41478

American (AMR) AF: 0.133 AC: 2026 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3468

East Asian (EAS) AF: 0.0979 AC: 507 AN: 5178

South Asian (SAS) AF: 0.185 AC: 890 AN: 4814

European-Finnish (FIN) AF: 0.138 AC: 1461 AN: 10554

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9912 AN: 67976

Other (OTH) AF: 0.156 AC: 328 AN: 2108

Alfa AF: 0.118 Hom.: 408

Bravo AF: 0.129

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Ehlers-Danlos syndrome, classic type, 2 (2)
-	-	2	not provided (2)
-	-	1	Ehlers-Danlos syndrome type 7A (1)
-	-	1	Ehlers-Danlos syndrome, classic type, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.0
DANN	Benign	0.79
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0015
dbscSNV1_RF	Benign	0.062
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: rs58106884; hg19: chr2-189953508; COSMIC: COSV66410277;