2-208121913-T-C

Position:

chr2-208121913-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006891.4(CRYGD):c.285A>G(p.Arg95Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 1,614,034 control chromosomes in the GnomAD database, including 649,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 58414 hom., cov: 32)

Exomes 𝑓: 0.90 ( 590683 hom. )

Consequence

CRYGD
NM_006891.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0270

Variant links:

Genes affected

CRYGD (HGNC:2411): (crystallin gamma D) Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Gamma-crystallins are a homogeneous group of highly symmetrical, monomeric proteins typically lacking connecting peptides and terminal extensions. They are differentially regulated after early development. Four gamma-crystallin genes (gamma-A through gamma-D) and three pseudogenes (gamma-E, gamma-F, gamma-G) are tandemly organized in a genomic segment as a gene cluster. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation. [provided by RefSeq, Jul 2008]

CRYGD links:

LOC100507443 (HGNC:):

LOC100507443 links:

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=-0.6).

BP6

Variant 2-208121913-T-C is Benign according to our data. Variant chr2-208121913-T-C is described in ClinVar as [Benign]. Clinvar id is 260061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-208121913-T-C is described in Lovd as [Benign]. Variant chr2-208121913-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.027 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYGD	NM_006891.4 linkuse as main transcript	c.285A>G	p.Arg95Arg	synonymous_variant	3/3	ENST00000264376.5	NP_008822.2	P07320A0A140CTX7
LOC100507443	NR_038437.1 linkuse as main transcript	n.97+2688T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGD	ENST00000264376.5 linkuse as main transcript	c.285A>G	p.Arg95Arg	synonymous_variant	3/3	1	NM_006891.4	ENSP00000264376.4		P07320

Frequencies

GnomAD3 genomes

AF:

0.873

AC:

132692

AN:

152064

Hom.:

58371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

0.971

Gnomad AMR

AF:

0.813

Gnomad ASJ

AF:

0.855

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.774

Gnomad FIN

AF:

0.924

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.922

Gnomad OTH

AF:

0.862

GnomAD3 exomes

AF:

0.847

AC:

212766

AN:

251086

Hom.:

91475

AF XY:

0.851

AC XY:

115497

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.843

Gnomad AMR exome

AF:

0.760

Gnomad ASJ exome

AF:

0.857

Gnomad EAS exome

AF:

0.577

Gnomad SAS exome

AF:

0.789

Gnomad FIN exome

AF:

0.922

Gnomad NFE exome

AF:

0.918

Gnomad OTH exome

AF:

0.873

GnomAD4 exome

AF:

0.896

AC:

1309645

AN:

1461852

Hom.:

590683

Cov.:

AF XY:

0.894

AC XY:

649914

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.841

Gnomad4 AMR exome

AF:

0.767

Gnomad4 ASJ exome

AF:

0.858

Gnomad4 EAS exome

AF:

0.557

Gnomad4 SAS exome

AF:

0.797

Gnomad4 FIN exome

AF:

0.923

Gnomad4 NFE exome

AF:

0.924

Gnomad4 OTH exome

AF:

0.873

GnomAD4 genome

AF:

0.873

AC:

132794

AN:

152182

Hom.:

58414

Cov.:

AF XY:

0.869

AC XY:

64663

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.847

Gnomad4 AMR

AF:

0.813

Gnomad4 ASJ

AF:

0.855

Gnomad4 EAS

AF:

0.593

Gnomad4 SAS

AF:

0.775

Gnomad4 FIN

AF:

0.924

Gnomad4 NFE

AF:

0.922

Gnomad4 OTH

AF:

0.859

Alfa

AF:

0.904

Hom.:

136343

Bravo

AF:

0.862

Asia WGS

AF:

0.653

AC:

2271

AN:

3478

EpiCase

AF:

0.916

EpiControl

AF:

0.915

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 4 multiple types

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Aculeiform cataract

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.8

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over