chr12-47995550-C-G

Variant names:

• chr12-47995550-C-G
• rs1793960
• NM_001844.5:c.708+160G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001844.5(COL2A1):​c.708+160G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,106 control chromosomes in the GnomAD database, including 1,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.16 (1939 hom., cov: 31)
• Consequence: COL2A1 NM_001844.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0900

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-47995550-C-G is Benign according to our data. Variant chr12-47995550-C-G is described in ClinVar as [Benign]. Clinvar id is 1183623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL2A1	NM_001844.5	c.708+160G>C		intron_variant	Intron 10 of 53	ENST00000380518.8	NP_001835.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL2A1	ENST00000380518.8	c.708+160G>C		intron_variant	Intron 10 of 53	1	NM_001844.5	ENSP00000369889.3
COL2A1	ENST00000337299.7	c.501+160G>C		intron_variant	Intron 9 of 52	1		ENSP00000338213.6

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23680 AN: 151988 Hom.: 1939 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.156 AC: 23677 AN: 152106 Hom.: 1939 Cov.: 31 AF XY: 0.155 AC XY: 11515 AN XY: 74344

African (AFR) AF: 0.131 AC: 5448 AN: 41490

American (AMR) AF: 0.105 AC: 1606 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 411 AN: 3468

East Asian (EAS) AF: 0.161 AC: 833 AN: 5160

South Asian (SAS) AF: 0.160 AC: 771 AN: 4812

European-Finnish (FIN) AF: 0.184 AC: 1948 AN: 10604

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12076 AN: 67970

Other (OTH) AF: 0.150 AC: 317 AN: 2108

Alfa AF: 0.166 Hom.: 271

Bravo AF: 0.149

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.61
Mutation Taster		=100/0	polymorphism (auto)

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: rs1793960; hg19: chr12-48389333; COSMIC: COSV61531367; COSMIC: COSV61531367;