chr2-208129538-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020989.4(CRYGC):​c.155A>C​(p.Gln52Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CRYGC
NM_020989.4 missense

Scores

1
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0990
Variant links:
Genes affected
CRYGC (HGNC:2410): (crystallin gamma C) This gene encodes a member of the beta/gamma-crystallin family of proteins. Crystallins constitute the major proteins of vertebrate eye lens and maintain the transparency and refractive index of the lens. This gene and several family members are present in a gene cluster on chromosome 2. Mutations in this gene have been shown to cause multiple types of cataract, including Coppock-like cataract and zonular pulverulent cataract, among others. [provided by RefSeq, Jan 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CRYGCNM_020989.4 linkc.155A>C p.Gln52Pro missense_variant 2/3 ENST00000282141.4 NP_066269.1 P07315A0A0X8GLL6
LOC100507443NR_038437.1 linkn.98-7518T>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CRYGCENST00000282141.4 linkc.155A>C p.Gln52Pro missense_variant 2/31 NM_020989.4 ENSP00000282141.3 P07315

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Nuclear pulverulent cataract Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 16, 2017This sequence change replaces glutamine with proline at codon 52 of the CRYGC protein (p.Gln52Pro). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CRYGC-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Benign
-0.019
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
17
DANN
Benign
0.94
DEOGEN2
Uncertain
0.60
D
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.12
N
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.52
D
MetaSVM
Benign
-0.73
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-2.0
N
REVEL
Uncertain
0.43
Sift
Benign
0.17
T
Sift4G
Benign
0.24
T
Polyphen
0.0040
B
Vest4
0.60
MutPred
0.54
Gain of glycosylation at Q52 (P = 0.0409);
MVP
0.76
MPC
0.13
ClinPred
0.27
T
GERP RS
-4.8
Varity_R
0.80
gMVP
0.66

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: rs1553585708; hg19: chr2-208994262; API