NM_000393.5:c.*1402T>G

Variant names:

• chr2-189032668-A-C
• rs11186
• NM_000393.5:c.*1402T>G

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.*1402T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 152,420 control chromosomes in the GnomAD database, including 720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (720 hom., cov: 32)
  • Exomes 𝑓: 0.087 (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: -0.00400
• Publications: 13 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=-0.87).
• BP6: Variant 2-189032668-A-C is Benign according to our data. Variant chr2-189032668-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 333106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	NM_000393.5	MANE Select	c.*1402T>G		3_prime_UTR	Exon 54 of 54	NP_000384.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	ENST00000374866.9	TSL:1 MANE Select	c.*1402T>G		3_prime_UTR	Exon 54 of 54	ENSP00000364000.3
	COL5A2	ENST00000618828.1	TSL:5	c.*1402T>G		3_prime_UTR	Exon 47 of 47	ENSP00000482184.1

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14522 AN: 152046 Hom.: 720 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0866 AC: 22 AN: 254 Hom.: 0 Cov.: 0 AF XY: 0.0671 AC XY: 11 AN XY: 164

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: 0.0887 AC: 22 AN: 248

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0955 AC: 14525 AN: 152166 Hom.: 720 Cov.: 32 AF XY: 0.0968 AC XY: 7203 AN XY: 74402

African (AFR) AF: 0.0725 AC: 3014 AN: 41552

American (AMR) AF: 0.0982 AC: 1498 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 598 AN: 3464

East Asian (EAS) AF: 0.103 AC: 534 AN: 5178

South Asian (SAS) AF: 0.150 AC: 722 AN: 4818

European-Finnish (FIN) AF: 0.0892 AC: 946 AN: 10606

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.101 AC: 6896 AN: 67978

Other (OTH) AF: 0.105 AC: 221 AN: 2110

Alfa AF: 0.106 Hom.: 1498

Bravo AF: 0.0937

Asia WGS AF: 0.124 AC: 429 AN: 3476

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	-0.87
CADD	Benign	2.1
DANN	Benign	0.67
PhyloP100		-0.0040
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: rs11186; hg19: chr2-189897394;