2-208121913-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

27 publications found

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 Gene-Disease associations (from GenCC):

cataract 4 multiple types
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
cataract - microcornea syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cerulean cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
coralliform cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset lamellar cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
pulverulent cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CRYGD links:

ENSG00000295187 (HGNC:):

ENSG00000295187 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 CliVar 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 CliVar as Benign. Clinvar id is 260061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
CRYGD	NM_006891.4 link	c.285A>G	p.Arg95Arg	synonymous_variant	Exon 3 of 3	ENST00000264376.5	NP_008822.2	P07320A0A140CTX7
LOC100507443	NR_038437.1 link	n.97+2688T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYGD	ENST00000264376.5 link	c.285A>G	p.Arg95Arg	synonymous_variant	Exon 3 of 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

GnomAD2 exomes

AF:

0.847

AC:

212766

AN:

251086

AF XY:

0.851

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 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

African (AFR)

AF:

0.841

AC:

28140

AN:

33480

American (AMR)

AF:

0.767

AC:

34321

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.858

AC:

22423

AN:

26136

East Asian (EAS)

AF:

0.557

AC:

22095

AN:

39700

South Asian (SAS)

AF:

0.797

AC:

68730

AN:

86254

European-Finnish (FIN)

AF:

0.923

AC:

49266

AN:

53404

Middle Eastern (MID)

AF:

0.829

AC:

4781

AN:

5768

European-Non Finnish (NFE)

AF:

0.924

AC:

1027157

AN:

1111990

Other (OTH)

AF:

0.873

AC:

52732

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

8015

16029

24044

32058

40073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21438

42876

64314

85752

107190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.873

AC:

132794

AN:

152182

Hom.:

58414

Cov.:

AF XY:

0.869

AC XY:

64663

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.847

AC:

35146

AN:

41516

American (AMR)

AF:

0.813

AC:

12427

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.855

AC:

2966

AN:

3468

East Asian (EAS)

AF:

0.593

AC:

3063

AN:

5164

South Asian (SAS)

AF:

0.775

AC:

3732

AN:

4814

European-Finnish (FIN)

AF:

0.924

AC:

9789

AN:

10590

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.922

AC:

62743

AN:

68020

Other (OTH)

AF:

0.859

AC:

1814

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

830

1660

2491

3321

4151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.900

Hom.:

252263

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

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 24, 2018

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aculeiform cataract

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.60

CADD

Benign

7.8

(source)

DANN

Benign

0.70

PhyloP100

-0.027

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over