rs41317929

chr12-47985625-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001844.5(COL2A1):c.1681-38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 1,612,190 control chromosomes in the GnomAD database, including 3,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (256 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3471 hom.)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.616

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 12-47985625-C-T is Benign according to our data. Variant chr12-47985625-C-T is described in ClinVar as [Benign]. Clinvar id is 258215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-47985625-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL2A1	NM_001844.5	c.1681-38G>A		intron_variant		ENST00000380518.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL2A1	ENST00000380518.8	c.1681-38G>A		intron_variant		1	NM_001844.5	P1
COL2A1	ENST00000337299.7	c.1474-38G>A		intron_variant		1
COL2A1	ENST00000493991.5	n.605-38G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7678 AN: 152090 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0290

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0864

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0446

GnomAD3 exomes AF: 0.0475 AC: 11898 AN: 250578 Hom.: 425 AF XY: 0.0469 AC XY: 6353 AN XY: 135494

Gnomad AFR exome AF: 0.0253

Gnomad AMR exome AF: 0.0181

Gnomad ASJ exome AF: 0.0114

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0113

Gnomad FIN exome AF: 0.0881

Gnomad NFE exome AF: 0.0726

Gnomad OTH exome AF: 0.0474

GnomAD4 exome AF: 0.0639 AC: 93277 AN: 1459982 Hom.: 3471 Cov.: 32 AF XY: 0.0623 AC XY: 45255 AN XY: 726424

Gnomad4 AFR exome AF: 0.0246

Gnomad4 AMR exome AF: 0.0196

Gnomad4 ASJ exome AF: 0.0121

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.0110

Gnomad4 FIN exome AF: 0.0877

Gnomad4 NFE exome AF: 0.0741

Gnomad4 OTH exome AF: 0.0540

GnomAD4 genome AF: 0.0505 AC: 7681 AN: 152208 Hom.: 256 Cov.: 32 AF XY: 0.0499 AC XY: 3714 AN XY: 74420

Gnomad4 AFR AF: 0.0276

Gnomad4 AMR AF: 0.0289

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.0864

Gnomad4 NFE AF: 0.0732

Gnomad4 OTH AF: 0.0441

Alfa AF: 0.0611 Hom.: 67

Bravo AF: 0.0436

Asia WGS AF: 0.0100 AC: 35 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

-

- -

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	-0.77
Cadd	Benign	2.2
Dann	Benign	0.80

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: rs41317929; hg19: chr12-48379408;