chr2-208124313-A-G

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.51T>C(p.Tyr17Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,608,444 control chromosomes in the GnomAD database, including 255,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28162 hom., cov: 33)

Exomes 𝑓: 0.56 ( 227463 hom. )

Consequence

CRYGD
NM_006891.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.446

Publications

16 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=-0.56).

BP6

Variant 2-208124313-A-G is Benign according to our data. Variant chr2-208124313-A-G is described in ClinVar as Benign. ClinVar VariationId is 260062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.446 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYGD	NM_006891.4 link	c.51T>C	p.Tyr17Tyr	synonymous_variant	Exon 2 of 3	ENST00000264376.5	NP_008822.2	P07320A0A140CTX7
LOC100507443	NR_038437.1 link	n.97+5088A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYGD	ENST00000264376.5 link	c.51T>C	p.Tyr17Tyr	synonymous_variant	Exon 2 of 3	1	NM_006891.4	ENSP00000264376.4		P07320

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91350

AN:

152014

Hom.:

28117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.723

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.704

Gnomad EAS

AF:

0.651

Gnomad SAS

AF:

0.743

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.619

GnomAD2 exomes

AF:

0.584

AC:

138623

AN:

237444

AF XY:

0.591

show subpopulations

Gnomad AFR exome

AF:

0.719

Gnomad AMR exome

AF:

0.504

Gnomad ASJ exome

AF:

0.702

Gnomad EAS exome

AF:

0.664

Gnomad FIN exome

AF:

0.530

Gnomad NFE exome

AF:

0.535

Gnomad OTH exome

AF:

0.575

GnomAD4 exome

AF:

0.555

AC:

808610

AN:

1456312

Hom.:

227463

Cov.:

AF XY:

0.561

AC XY:

405857

AN XY:

724068

show subpopulations

African (AFR)

AF:

0.729

AC:

24374

AN:

33432

American (AMR)

AF:

0.505

AC:

22122

AN:

43776

Ashkenazi Jewish (ASJ)

AF:

0.705

AC:

18320

AN:

25980

East Asian (EAS)

AF:

0.652

AC:

25754

AN:

39476

South Asian (SAS)

AF:

0.733

AC:

62810

AN:

85714

European-Finnish (FIN)

AF:

0.528

AC:

27649

AN:

52344

Middle Eastern (MID)

AF:

0.686

AC:

3938

AN:

5742

European-Non Finnish (NFE)

AF:

0.530

AC:

588259

AN:

1109678

Other (OTH)

AF:

0.588

AC:

35384

AN:

60170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

21974

43948

65921

87895

109869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17016

34032

51048

68064

85080

<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:

0.601

AC:

91445

AN:

152132

Hom.:

28162

Cov.:

AF XY:

0.604

AC XY:

44932

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.724

AC:

30078

AN:

41542

American (AMR)

AF:

0.546

AC:

8339

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.704

AC:

2444

AN:

3472

East Asian (EAS)

AF:

0.651

AC:

3355

AN:

5156

South Asian (SAS)

AF:

0.741

AC:

3570

AN:

4816

European-Finnish (FIN)

AF:

0.536

AC:

5670

AN:

10586

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.532

AC:

36165

AN:

67968

Other (OTH)

AF:

0.622

AC:

1312

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1885

3770

5654

7539

9424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<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:

0.576

Hom.:

12658

Bravo

AF:

0.604

Asia WGS

AF:

0.708

AC:

2461

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Cataract 4 multiple types

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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. -

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

-0.56

CADD

Benign

6.2

(source)

DANN

Benign

0.67

PhyloP100

0.45

PromoterAI

0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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