rs5837121

Variant names:

• chr2-189058904-ATTTT-A
• rs5837121
• NM_000393.5:c.2086-15_2086-12delAAAA

Your query was ambiguous. Multiple possible variants found:

• chr2-189058904-ATTTT-A
• chr2-189058904-ATTTT-AT
• chr2-189058904-ATTTT-ATT
• chr2-189058904-ATTTT-ATTT
• chr2-189058904-ATTTT-ATTTTT
• chr2-189058904-ATTTT-ATTTTTT
• chr2-189058904-ATTTT-ATTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000393.5(COL5A2):​c.2086-15_2086-12delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000721 in 1,249,082 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 8 AD gene.

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.2086-15_2086-12delAAAA		intron	N/A	NP_000384.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	ENST00000374866.9	TSL:1 MANE Select	c.2086-15_2086-12delAAAA		intron	N/A	ENSP00000364000.3
	COL5A2	ENST00000618828.1	TSL:5	c.925-15_925-12delAAAA		intron	N/A	ENSP00000482184.1
	COL5A2	ENST00000470524.2	TSL:5	n.192-15_192-12delAAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000669 AC: 1 AN: 149582 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000728 AC: 8 AN: 1099500 Hom.: 0 AF XY: 0.00000907 AC XY: 5 AN XY: 551104

African (AFR) AF: 0.00 AC: 0 AN: 28164

American (AMR) AF: 0.00 AC: 0 AN: 38296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20100

East Asian (EAS) AF: 0.00 AC: 0 AN: 33258

South Asian (SAS) AF: 0.00 AC: 0 AN: 69868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4882

European-Non Finnish (NFE) AF: 0.00000859 AC: 7 AN: 814810

Other (OTH) AF: 0.0000217 AC: 1 AN: 46172

GnomAD4 genome AF: 0.00000669 AC: 1 AN: 149582 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72918

African (AFR) AF: 0.00 AC: 0 AN: 40806

American (AMR) AF: 0.00 AC: 0 AN: 15002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00 AC: 0 AN: 4746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67304

Other (OTH) AF: 0.00 AC: 0 AN: 2046

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5837121; hg19: chr2-189923630;