rs41317933

chr12-47985117-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001844.5(COL2A1):c.1735-24T>C variant causes a intron change. The variant allele was found at a frequency of 0.063 in 1,582,242 control chromosomes in the GnomAD database, including 3,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (247 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3405 hom.)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.74

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 12-47985117-A-G is Benign according to our data. Variant chr12-47985117-A-G is described in ClinVar as [Benign]. Clinvar id is 258216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL2A1	NM_001844.5	c.1735-24T>C		intron_variant		ENST00000380518.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL2A1	ENST00000380518.8	c.1735-24T>C		intron_variant		1	NM_001844.5	P1
COL2A1	ENST00000337299.7	c.1528-24T>C		intron_variant		1
COL2A1	ENST00000493991.5	n.659-24T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7685 AN: 152078 Hom.: 247 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0292

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0735

Gnomad OTH AF: 0.0455

GnomAD3 exomes AF: 0.0482 AC: 11495 AN: 238680 Hom.: 394 AF XY: 0.0476 AC XY: 6174 AN XY: 129650

Gnomad AFR exome AF: 0.0243

Gnomad AMR exome AF: 0.0193

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.000282

Gnomad SAS exome AF: 0.0116

Gnomad FIN exome AF: 0.0889

Gnomad NFE exome AF: 0.0740

Gnomad OTH exome AF: 0.0500

GnomAD4 exome AF: 0.0643 AC: 91991 AN: 1430046 Hom.: 3405 Cov.: 26 AF XY: 0.0628 AC XY: 44728 AN XY: 712670

Gnomad4 AFR exome AF: 0.0230

Gnomad4 AMR exome AF: 0.0210

Gnomad4 ASJ exome AF: 0.0128

Gnomad4 EAS exome AF: 0.000432

Gnomad4 SAS exome AF: 0.0115

Gnomad4 FIN exome AF: 0.0879

Gnomad4 NFE exome AF: 0.0747

Gnomad4 OTH exome AF: 0.0547

GnomAD4 genome AF: 0.0505 AC: 7691 AN: 152196 Hom.: 247 Cov.: 32 AF XY: 0.0500 AC XY: 3717 AN XY: 74396

Gnomad4 AFR AF: 0.0270

Gnomad4 AMR AF: 0.0291

Gnomad4 ASJ AF: 0.0113

Gnomad4 EAS AF: 0.000775

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.0861

Gnomad4 NFE AF: 0.0735

Gnomad4 OTH AF: 0.0450

Alfa AF: 0.0674 Hom.: 175

Bravo AF: 0.0436

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	12
Dann	Benign	0.76

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: rs41317933; hg19: chr12-48378900;