rs1793953

chr12-47999743-G-Achr12-47999743-G-Cchr12-47999743-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001844.5(COL2A1):c.292+176C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 614,208 control chromosomes in the GnomAD database, including 114,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (23292 hom., cov: 27)
  • Exomes 𝑓: 0.62 (91489 hom.)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.09

Genes affected

COL2A1 (HGNC:2200): (collagen type II alpha 1 chain) This gene encodes the alpha-1 chain of type II collagen, a fibrillar collagen found in cartilage and the vitreous humor of the eye. Mutations in this gene are associated with achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome type I, and spondyloepimetaphyseal dysplasia Strudwick type. In addition, defects in processing chondrocalcin, a calcium binding protein that is the C-propeptide of this collagen molecule, are also associated with chondrodysplasia. There are two transcripts identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 12-47999743-G-A is Benign according to our data. Variant chr12-47999743-G-A is described in ClinVar as [Benign]. Clinvar id is 677851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL2A1	NM_001844.5	c.292+176C>T		intron_variant		ENST00000380518.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL2A1	ENST00000380518.8	c.292+176C>T		intron_variant		1	NM_001844.5	P1
COL2A1	ENST00000337299.7	c.86-1312C>T		intron_variant		1
COL2A1	ENST00000490609.2	n.701C>T		non_coding_transcript_exon_variant	2/2	2
COL2A1	ENST00000474996.6	n.530+176C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.530 AC: 79186 AN: 149516 Hom.: 23292 Cov.: 27

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.593

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.620 AC: 287828 AN: 464566 Hom.: 91489 Cov.: 4 AF XY: 0.621 AC XY: 153067 AN XY: 246480

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.487

Gnomad4 ASJ exome AF: 0.672

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.597

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.677

Gnomad4 OTH exome AF: 0.617

GnomAD4 genome AF: 0.529 AC: 79222 AN: 149642 Hom.: 23292 Cov.: 27 AF XY: 0.527 AC XY: 38407 AN XY: 72876

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.561

Alfa AF: 0.612 Hom.: 11497

Bravo AF: 0.505

Asia WGS AF: 0.476 AC: 1659 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.018
Dann	Benign	0.33

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: rs1793953; hg19: chr12-48393526; COSMIC: COSV61531117; COSMIC: COSV61531117;