rs1793949

chr12-47977812-G-Achr12-47977812-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001844.5(COL2A1):c.3112-159C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,008 control chromosomes in the GnomAD database, including 10,021 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (10021 hom., cov: 32)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.359

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-47977812-G-A is Benign according to our data. Variant chr12-47977812-G-A is described in ClinVar as [Benign]. Clinvar id is 1181380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL2A1	NM_001844.5	c.3112-159C>T		intron_variant		ENST00000380518.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL2A1	ENST00000380518.8	c.3112-159C>T		intron_variant		1	NM_001844.5	P1
COL2A1	ENST00000337299.7	c.2905-159C>T		intron_variant		1
COL2A1	ENST00000493991.5	n.2198-159C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51505 AN: 151890 Hom.: 10021 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.339 AC: 51505 AN: 152008 Hom.: 10021 Cov.: 32 AF XY: 0.333 AC XY: 24750 AN XY: 74274

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.382

Alfa AF: 0.420 Hom.: 18815

Bravo AF: 0.331

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.4
Dann	Benign	0.41

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: rs1793949; hg19: chr12-48371595;