rs760530147

chr12-47987735-TGAA-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001844.5(COL2A1):c.1123-29_1123-27del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,577,276 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (3 hom.)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.840

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-47987735-TGAA-T is Benign according to our data. Variant chr12-47987735-TGAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 258205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL2A1	NM_001844.5	c.1123-29_1123-27del		intron_variant		ENST00000380518.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL2A1	ENST00000380518.8	c.1123-29_1123-27del		intron_variant		1	NM_001844.5	P1
COL2A1	ENST00000337299.7	c.916-29_916-27del		intron_variant		1
COL2A1	ENST00000493991.5	n.47-29_47-27del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000231 AC: 35 AN: 151808 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000401 AC: 86 AN: 214522 Hom.: 1 AF XY: 0.000379 AC XY: 44 AN XY: 116050

Gnomad AFR exome AF: 0.0000781

Gnomad AMR exome AF: 0.000154

Gnomad ASJ exome AF: 0.00621

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000914

GnomAD4 exome AF: 0.000267 AC: 380 AN: 1425468 Hom.: 3 AF XY: 0.000282 AC XY: 200 AN XY: 708518

Gnomad4 AFR exome AF: 0.0000614

Gnomad4 AMR exome AF: 0.000139

Gnomad4 ASJ exome AF: 0.00632

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000171

Gnomad4 OTH exome AF: 0.000390

GnomAD4 genome AF: 0.000231 AC: 35 AN: 151808 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74106

Gnomad4 AFR AF: 0.000194

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00126 Hom.: 0

Bravo AF: 0.000246

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

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: rs760530147; hg19: chr12-48381518;