rs1635547

Positions:

• chr12-47986178-A-C

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.1527+158T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,724 control chromosomes in the GnomAD database, including 16,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.47 (16988 hom., cov: 32)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.334

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=-0.83).
• BP6: Variant 12-47986178-A-C is Benign according to our data. Variant chr12-47986178-A-C is described in ClinVar as [Benign]. Clinvar id is 585506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL2A1	NM_001844.5	c.1527+158T>G		intron_variant		ENST00000380518.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL2A1	ENST00000380518.8	c.1527+158T>G		intron_variant		1	NM_001844.5	P1
COL2A1	ENST00000337299.7	c.1320+158T>G		intron_variant		1
COL2A1	ENST00000493991.5	n.451+158T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71305 AN: 151604 Hom.: 16976 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.470 AC: 71339 AN: 151724 Hom.: 16988 Cov.: 32 AF XY: 0.466 AC XY: 34555 AN XY: 74120

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.467

Alfa AF: 0.469 Hom.: 2113

Bravo AF: 0.467

Asia WGS AF: 0.465 AC: 1616 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	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.56

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: rs1635547; hg19: chr12-48379961; COSMIC: COSV61530632; COSMIC: COSV61530632;