chr12-47989452-A-G

Position:

• chr12-47989452-A-G

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.1069-171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,898 control chromosomes in the GnomAD database, including 18,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.49 (18378 hom., cov: 32)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.72

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=-0.93).
• BP6: Variant 12-47989452-A-G is Benign according to our data. Variant chr12-47989452-A-G is described in ClinVar as [Benign]. Clinvar id is 1268186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL2A1	NM_001844.5	c.1069-171T>C		intron_variant		ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8	c.1069-171T>C		intron_variant		1	NM_001844.5	ENSP00000369889.3
COL2A1	ENST00000337299.7	c.862-171T>C		intron_variant		1		ENSP00000338213.6

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73974 AN: 151780 Hom.: 18362 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.487 AC: 74019 AN: 151898 Hom.: 18378 Cov.: 32 AF XY: 0.484 AC XY: 35914 AN XY: 74214

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.476

Alfa AF: 0.480 Hom.: 2219

Bravo AF: 0.485

Asia WGS AF: 0.467 AC: 1621 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 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.39
DANN	Benign	0.32

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: rs1635537; hg19: chr12-48383235;