rs41263845

chr12-47984164-G-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.1888-24C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,610,096 control chromosomes in the GnomAD database, including 3,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (255 hom., cov: 33)
  • Exomes 𝑓: 0.066 (3658 hom.)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.52

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=-0.94).
• BP6: Variant 12-47984164-G-T is Benign according to our data. Variant chr12-47984164-G-T is described in ClinVar as [Benign]. Clinvar id is 258218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL2A1	NM_001844.5	c.1888-24C>A		intron_variant		ENST00000380518.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL2A1	ENST00000380518.8	c.1888-24C>A		intron_variant		1	NM_001844.5	P1
COL2A1	ENST00000337299.7	c.1681-24C>A		intron_variant		1
COL2A1	ENST00000493991.5	n.812-24C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7597 AN: 152144 Hom.: 256 Cov.: 33

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.0860

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0473

GnomAD3 exomes AF: 0.0484 AC: 11873 AN: 245222 Hom.: 417 AF XY: 0.0481 AC XY: 6396 AN XY: 132848

Gnomad AFR exome AF: 0.0175

Gnomad AMR exome AF: 0.0207

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.000275

Gnomad SAS exome AF: 0.0115

Gnomad FIN exome AF: 0.0870

Gnomad NFE exome AF: 0.0746

Gnomad OTH exome AF: 0.0501

GnomAD4 exome AF: 0.0660 AC: 96154 AN: 1457834 Hom.: 3658 Cov.: 33 AF XY: 0.0644 AC XY: 46671 AN XY: 725032

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.0226

Gnomad4 ASJ exome AF: 0.0176

Gnomad4 EAS exome AF: 0.000429

Gnomad4 SAS exome AF: 0.0114

Gnomad4 FIN exome AF: 0.0871

Gnomad4 NFE exome AF: 0.0766

Gnomad4 OTH exome AF: 0.0564

GnomAD4 genome AF: 0.0499 AC: 7599 AN: 152262 Hom.: 255 Cov.: 33 AF XY: 0.0497 AC XY: 3699 AN XY: 74452

Gnomad4 AFR AF: 0.0203

Gnomad4 AMR AF: 0.0303

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.0860

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.0468

Alfa AF: 0.0623 Hom.: 71

Bravo AF: 0.0429

Asia WGS AF: 0.0120 AC: 43 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	-0.94
Cadd	Benign	0.0040
Dann	Benign	0.29

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: rs41263845; hg19: chr12-48377947;