rs56380683

Variant names:

• chr2-189100165-A-G
• rs56380683
• NM_000393.5:c.337-26T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-189100165-A-G
• chr2-189100165-A-C

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.337-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,596,518 control chromosomes in the GnomAD database, including 16,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1368 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15444 hom.)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -5.71
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 2-189100165-A-G is Benign according to our data. Variant chr2-189100165-A-G is described in ClinVar as Benign. ClinVar VariationId is 256000.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.337-26T>C		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.337-26T>C		intron	N/A	ENSP00000364000.3	P05997
	COL5A2	ENST00000858728.1		c.334-26T>C		intron	N/A	ENSP00000528787.1
	COL5A2	ENST00000858729.1		c.337-26T>C		intron	N/A	ENSP00000528788.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20196 AN: 151996 Hom.: 1371 Cov.: 32

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0978

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.141 AC: 35211 AN: 250192 AF XY: 0.147

Gnomad AFR exome AF: 0.0949

Gnomad AMR exome AF: 0.0947

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.0960

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.142 AC: 205174 AN: 1444404 Hom.: 15444 Cov.: 27 AF XY: 0.145 AC XY: 103996 AN XY: 719470

African (AFR) AF: 0.0916 AC: 3036 AN: 33134

American (AMR) AF: 0.102 AC: 4556 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 5855 AN: 25970

East Asian (EAS) AF: 0.111 AC: 4380 AN: 39488

South Asian (SAS) AF: 0.187 AC: 16064 AN: 85772

European-Finnish (FIN) AF: 0.141 AC: 7539 AN: 53308

Middle Eastern (MID) AF: 0.243 AC: 1387 AN: 5710

European-Non Finnish (NFE) AF: 0.140 AC: 153517 AN: 1096602

Other (OTH) AF: 0.148 AC: 8840 AN: 59758

GnomAD4 genome AF: 0.133 AC: 20189 AN: 152114 Hom.: 1368 Cov.: 32 AF XY: 0.134 AC XY: 9957 AN XY: 74370

African (AFR) AF: 0.0982 AC: 4076 AN: 41518

American (AMR) AF: 0.132 AC: 2020 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3472

East Asian (EAS) AF: 0.0973 AC: 504 AN: 5180

South Asian (SAS) AF: 0.185 AC: 892 AN: 4824

European-Finnish (FIN) AF: 0.137 AC: 1454 AN: 10586

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

European-Non Finnish (NFE) AF: 0.146 AC: 9914 AN: 67960

Other (OTH) AF: 0.155 AC: 327 AN: 2110

Alfa AF: 0.147 Hom.: 347

Bravo AF: 0.129

Asia WGS AF: 0.137 AC: 474 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.013
DANN	Benign	0.31
PhyloP100		-5.7
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: rs56380683; hg19: chr2-189964891; COSMIC: COSV66410283; COSMIC: COSV66410283;