12-47995462-C-T

Position:

• chr12-47995462-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.709-154G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,152 control chromosomes in the GnomAD database, including 3,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.20 (3272 hom., cov: 32)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.02

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=-0.87).
• BP6: Variant 12-47995462-C-T is Benign according to our data. Variant chr12-47995462-C-T is described in ClinVar as [Benign]. Clinvar id is 1258807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL2A1	NM_001844.5	c.709-154G>A		intron_variant		ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8	c.709-154G>A		intron_variant		1	NM_001844.5	ENSP00000369889.3
COL2A1	ENST00000337299.7	c.502-154G>A		intron_variant		1		ENSP00000338213.6

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30289 AN: 152032 Hom.: 3267 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30308 AN: 152152 Hom.: 3272 Cov.: 32 AF XY: 0.197 AC XY: 14628 AN XY: 74376

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.182

Alfa AF: 0.171 Hom.: 3098

Bravo AF: 0.198

Asia WGS AF: 0.161 AC: 561 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.92

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: rs12423250; hg19: chr12-48389245;