chr2-189110232-G-T

Position:

• chr2-189110232-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000393.5(COL5A2):​c.315C>A​(p.Thr105Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 1,612,522 control chromosomes in the GnomAD database, including 746,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66285 hom., cov: 31)
  • Exomes 𝑓: 0.96 (680320 hom.)
• Consequence: COL5A2 NM_000393.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.524

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-189110232-G-T is Benign according to our data. Variant chr2-189110232-G-T is described in ClinVar as [Benign]. Clinvar id is 439539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.524 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.315C>A	p.Thr105Thr	synonymous_variant	2/54	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.177C>A	p.Thr59Thr	synonymous_variant	5/57		XP_011508875.1
COL5A2	XM_047443251.1	c.177C>A	p.Thr59Thr	synonymous_variant	7/59		XP_047299207.1
COL5A2	XM_047443252.1	c.177C>A	p.Thr59Thr	synonymous_variant	6/58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.315C>A	p.Thr105Thr	synonymous_variant	2/54	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000649966.1	c.177C>A	p.Thr59Thr	synonymous_variant	2/11			ENSP00000496785.1
COL5A2	ENST00000618828.1	c.-316C>A		5_prime_UTR_variant	2/47	5		ENSP00000482184.1

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141673 AN: 152098 Hom.: 66260 Cov.: 31

Gnomad AFR AF: 0.857

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.931

GnomAD3 exomes AF: 0.930 AC: 233806 AN: 251280 Hom.: 109454 AF XY: 0.935 AC XY: 126976 AN XY: 135824

Gnomad AFR exome AF: 0.856

Gnomad AMR exome AF: 0.799

Gnomad ASJ exome AF: 0.969

Gnomad EAS exome AF: 0.918

Gnomad SAS exome AF: 0.887

Gnomad FIN exome AF: 0.988

Gnomad NFE exome AF: 0.980

Gnomad OTH exome AF: 0.943

GnomAD4 exome AF: 0.964 AC: 1407881 AN: 1460306 Hom.: 680320 Cov.: 34 AF XY: 0.963 AC XY: 699557 AN XY: 726558

Gnomad4 AFR exome AF: 0.853

Gnomad4 AMR exome AF: 0.805

Gnomad4 ASJ exome AF: 0.969

Gnomad4 EAS exome AF: 0.869

Gnomad4 SAS exome AF: 0.890

Gnomad4 FIN exome AF: 0.988

Gnomad4 NFE exome AF: 0.982

Gnomad4 OTH exome AF: 0.955

GnomAD4 genome AF: 0.931 AC: 141747 AN: 152216 Hom.: 66285 Cov.: 31 AF XY: 0.931 AC XY: 69255 AN XY: 74424

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.889

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.981

Gnomad4 OTH AF: 0.930

Alfa AF: 0.968 Hom.: 84217

Bravo AF: 0.918

Asia WGS AF: 0.897 AC: 3121 AN: 3478

EpiCase AF: 0.979

EpiControl AF: 0.976

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Ehlers-Danlos syndrome, classic type, 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.9
DANN	Benign	0.66

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: rs4128539; hg19: chr2-189974958;