rs10165260

Variant names:

• chr2-189087906-G-A
• rs10165260
• NM_000393.5:c.645+789C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-189087906-G-A
• chr2-189087906-G-C
• chr2-189087906-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000393.5(COL5A2):​c.645+789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 151,690 control chromosomes in the GnomAD database, including 57,508 homozygotes. 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: 𝑓 0.86 (57508 hom., cov: 31)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.948 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.645+789C>T		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.645+789C>T		intron	N/A	ENSP00000364000.3	P05997
	COL5A2	ENST00000858728.1		c.642+789C>T		intron	N/A	ENSP00000528787.1
	COL5A2	ENST00000858729.1		c.645+789C>T		intron	N/A	ENSP00000528788.1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 130989 AN: 151572 Hom.: 57495 Cov.: 31

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.871

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.864 AC: 131046 AN: 151690 Hom.: 57508 Cov.: 31 AF XY: 0.863 AC XY: 64027 AN XY: 74150

African (AFR) AF: 0.706 AC: 29187 AN: 41340

American (AMR) AF: 0.821 AC: 12513 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3293 AN: 3466

East Asian (EAS) AF: 0.814 AC: 4216 AN: 5178

South Asian (SAS) AF: 0.848 AC: 4087 AN: 4822

European-Finnish (FIN) AF: 0.959 AC: 9984 AN: 10416

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64790 AN: 67912

Other (OTH) AF: 0.870 AC: 1833 AN: 2106

Alfa AF: 0.895 Hom.: 19296

Bravo AF: 0.845

Asia WGS AF: 0.782 AC: 2713 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.030
DANN	Benign	0.14
PhyloP100		-1.7
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: rs10165260; hg19: chr2-189952632;