rs878967711

Positions:

• chr2-189058904-ATT-A
• chr2-189058904-A-ATTTTTTTTTTTTT
• chr2-189058904-A-AT
• chr2-189058904-ATTTT-A
• chr2-189058904-AT-A
• chr2-189058904-ATTT-A
• chr2-189058904-A-ATT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000393.5(COL5A2):​c.2086-13_2086-12del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,055,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00089 (0 hom., cov: 0)
  • Exomes 𝑓: 0.039 (0 hom.)
• Consequence: COL5A2 NM_000393.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.50

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-189058904-ATT-A is Benign according to our data. Variant chr2-189058904-ATT-A is described in ClinVar as [Benign]. Clinvar id is 517024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-189058904-ATT-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.039 (35320/905650) while in subpopulation NFE AF= 0.0416 (27760/667576). AF 95% confidence interval is 0.0412. There are 0 homozygotes in gnomad4_exome. There are 17290 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A2	NM_000393.5	c.2086-13_2086-12del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000374866.9
COL5A2	XM_011510573.4	c.1948-13_1948-12del		splice_polypyrimidine_tract_variant, intron_variant
COL5A2	XM_047443251.1	c.1948-13_1948-12del		splice_polypyrimidine_tract_variant, intron_variant
COL5A2	XM_047443252.1	c.1948-13_1948-12del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A2	ENST00000374866.9	c.2086-13_2086-12del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000393.5	P1
COL5A2	ENST00000618828.1	c.925-13_925-12del		splice_polypyrimidine_tract_variant, intron_variant		5
COL5A2	ENST00000470524.2	n.192-13_192-12del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.000891 AC: 133 AN: 149268 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000267

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000633

Gnomad FIN AF: 0.00234

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000715

Gnomad OTH AF: 0.00147

GnomAD4 exome AF: 0.0390 AC: 35320 AN: 905650 Hom.: 0 AF XY: 0.0383 AC XY: 17290 AN XY: 450870

Gnomad4 AFR exome AF: 0.0208

Gnomad4 AMR exome AF: 0.0292

Gnomad4 ASJ exome AF: 0.0419

Gnomad4 EAS exome AF: 0.0247

Gnomad4 SAS exome AF: 0.0380

Gnomad4 FIN exome AF: 0.0272

Gnomad4 NFE exome AF: 0.0416

Gnomad4 OTH exome AF: 0.0381

GnomAD4 genome AF: 0.000890 AC: 133 AN: 149376 Hom.: 0 Cov.: 0 AF XY: 0.000865 AC XY: 63 AN XY: 72854

Gnomad4 AFR AF: 0.00122

Gnomad4 AMR AF: 0.000267

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.000633

Gnomad4 FIN AF: 0.00234

Gnomad4 NFE AF: 0.000715

Gnomad4 OTH AF: 0.00146

Alfa AF: 0.107 Hom.: 2945

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Ehlers-Danlos syndrome, classic type, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs5837121; hg19: chr2-189923630;