rs115270781

Variant names:

• chr12-47985711-G-A
• rs115270781
• NM_001844.5:c.1680+17C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001844.5(COL2A1):​c.1680+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,613,258 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (43 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (40 hom.)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.21

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=-0.81).
• BP6: Variant 12-47985711-G-A is Benign according to our data. Variant chr12-47985711-G-A is described in ClinVar as [Benign]. Clinvar id is 258214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-47985711-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1849/152256) while in subpopulation AFR AF= 0.0414 (1719/41540). AF 95% confidence interval is 0.0398. There are 43 homozygotes in gnomad4. There are 840 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1849 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL2A1	NM_001844.5	c.1680+17C>T		intron_variant	Intron 25 of 53	ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8	c.1680+17C>T		intron_variant	Intron 25 of 53	1	NM_001844.5	ENSP00000369889.3
COL2A1	ENST00000337299.7	c.1473+17C>T		intron_variant	Intron 24 of 52	1		ENSP00000338213.6
COL2A1	ENST00000493991.5	n.604+17C>T		intron_variant	Intron 8 of 36	2

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1843 AN: 152138 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00333 AC: 833 AN: 250352 Hom.: 19 AF XY: 0.00247 AC XY: 335 AN XY: 135434

Gnomad AFR exome AF: 0.0429

Gnomad AMR exome AF: 0.00261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000292

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00130 AC: 1897 AN: 1461002 Hom.: 40 Cov.: 33 AF XY: 0.00117 AC XY: 848 AN XY: 726890

Gnomad4 AFR exome AF: 0.0412

Gnomad4 AMR exome AF: 0.00295

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000156

Gnomad4 OTH exome AF: 0.00258

GnomAD4 genome AF: 0.0121 AC: 1849 AN: 152256 Hom.: 43 Cov.: 32 AF XY: 0.0113 AC XY: 840 AN XY: 74434

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00688 Hom.: 3

Bravo AF: 0.0138

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 30, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 14, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	17
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: rs115270781; hg19: chr12-48379494;