rs56380683

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000393.5(COL5A2):​c.337-26T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000691 in 1,448,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Not reported in ClinVar
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00000691 (10/1448200) while in subpopulation SAS AF = 0.000105 (9/85892). AF 95% confidence interval is 0.0000542. There are 0 homozygotes in GnomAdExome4. There are 6 alleles in the male GnomAdExome4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.337-26T>G		intron_variant	Intron 3 of 53	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.199-26T>G		intron_variant	Intron 6 of 56		XP_011508875.1
COL5A2	XM_047443251.1	c.199-26T>G		intron_variant	Intron 8 of 58		XP_047299207.1
COL5A2	XM_047443252.1	c.199-26T>G		intron_variant	Intron 7 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.337-26T>G		intron_variant	Intron 3 of 53	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.-294-26T>G		intron_variant	Intron 3 of 46	5		ENSP00000482184.1
COL5A2	ENST00000649966.1	c.199-26T>G		intron_variant	Intron 3 of 10			ENSP00000496785.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250192 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000691 AC: 10 AN: 1448200 Hom.: 0 Cov.: 27 AF XY: 0.00000832 AC XY: 6 AN XY: 721242

African (AFR) AF: 0.00 AC: 0 AN: 33188

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39506

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100010

Other (OTH) AF: 0.00 AC: 0 AN: 59870

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000348 Hom.: 347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.022
DANN	Benign	0.35
PhyloP100		-5.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;