12-47973422-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001844.5(COL2A1):​c.4449G>A​(p.Pro1483Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000612 in 1,614,074 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 2 hom. )

Consequence

COL2A1
NM_001844.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.397
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 12-47973422-C-T is Benign according to our data. Variant chr12-47973422-C-T is described in ClinVar as [Benign]. Clinvar id is 516233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.397 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00327 (497/152180) while in subpopulation AFR AF= 0.0112 (463/41492). AF 95% confidence interval is 0.0103. There are 3 homozygotes in gnomad4. There are 223 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 497 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL2A1NM_001844.5 linkc.4449G>A p.Pro1483Pro synonymous_variant Exon 54 of 54 ENST00000380518.8 NP_001835.3 P02458-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL2A1ENST00000380518.8 linkc.4449G>A p.Pro1483Pro synonymous_variant Exon 54 of 54 1 NM_001844.5 ENSP00000369889.3 P02458-2
COL2A1ENST00000337299.7 linkc.4242G>A p.Pro1414Pro synonymous_variant Exon 53 of 53 1 ENSP00000338213.6 P02458-1
COL2A1ENST00000493991.5 linkn.3535G>A non_coding_transcript_exon_variant Exon 37 of 37 2

Frequencies

GnomAD3 genomes
AF:
0.00327
AC:
498
AN:
152062
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0112
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00137
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000847
AC:
213
AN:
251494
Hom.:
2
AF XY:
0.000537
AC XY:
73
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.0118
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000439
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000336
AC:
491
AN:
1461894
Hom.:
2
Cov.:
31
AF XY:
0.000300
AC XY:
218
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0117
Gnomad4 AMR exome
AF:
0.000738
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000252
Gnomad4 OTH exome
AF:
0.000629
GnomAD4 genome
AF:
0.00327
AC:
497
AN:
152180
Hom.:
3
Cov.:
32
AF XY:
0.00300
AC XY:
223
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.0112
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00164
Hom.:
1
Bravo
AF:
0.00378
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jan 25, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Aug 24, 2020
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:1
Dec 06, 2017
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Connective tissue disorder Benign:1
Nov 01, 2021
Genome Diagnostics Laboratory, The Hospital for Sick Children
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
-0.65
CADD
Benign
8.8
DANN
Benign
0.85

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs41272771; hg19: chr12-48367205; COSMIC: COSV56742985; COSMIC: COSV56742985; API