rs3829735

chr12-47982816-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.2193+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,581,386 control chromosomes in the GnomAD database, including 945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (68 hom., cov: 33)
  • Exomes 𝑓: 0.012 (877 hom.)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.50

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]

LOC105369752 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-47982816-C-T is Benign according to our data. Variant chr12-47982816-C-T is described in ClinVar as [Benign]. Clinvar id is 258224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL2A1	NM_001844.5	c.2193+32G>A		intron_variant		ENST00000380518.8
LOC105369752	XR_944910.2	n.298C>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL2A1	ENST00000380518.8	c.2193+32G>A		intron_variant		1	NM_001844.5	P1
COL2A1	ENST00000337299.7	c.1986+32G>A		intron_variant		1
COL2A1	ENST00000483376.1	n.371+32G>A		intron_variant, non_coding_transcript_variant		5
COL2A1	ENST00000493991.5	n.1117+32G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1753 AN: 152180 Hom.: 69 Cov.: 33

Gnomad AFR AF: 0.00883

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00536

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00237

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.0254 AC: 6193 AN: 243420 Hom.: 350 AF XY: 0.0301 AC XY: 3986 AN XY: 132480

Gnomad AFR exome AF: 0.00967

Gnomad AMR exome AF: 0.00313

Gnomad ASJ exome AF: 0.00890

Gnomad EAS exome AF: 0.108

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.0000604

Gnomad NFE exome AF: 0.00286

Gnomad OTH exome AF: 0.0174

GnomAD4 exome AF: 0.0120 AC: 17093 AN: 1429088 Hom.: 877 Cov.: 30 AF XY: 0.0151 AC XY: 10788 AN XY: 712968

Gnomad4 AFR exome AF: 0.00856

Gnomad4 AMR exome AF: 0.00331

Gnomad4 ASJ exome AF: 0.00951

Gnomad4 EAS exome AF: 0.0955

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.000108

Gnomad4 NFE exome AF: 0.00148

Gnomad4 OTH exome AF: 0.0183

GnomAD4 genome AF: 0.0115 AC: 1750 AN: 152298 Hom.: 68 Cov.: 33 AF XY: 0.0141 AC XY: 1053 AN XY: 74476

Gnomad4 AFR AF: 0.00883

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.0996

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00238

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.00725 Hom.: 7

Bravo AF: 0.00997

Asia WGS AF: 0.0780 AC: 271 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 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.057
Dann	Benign	0.49

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: rs3829735; hg19: chr12-48376599; COSMIC: COSV61531114;