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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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 ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006891.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYGD	NM_006891.4	MANE Select	c.285A>G	p.Arg95Arg	synonymous	Exon 3 of 3	NP_008822.2
	LOC100507443	NR_038437.1		n.97+2688T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRYGD	ENST00000264376.5	TSL:1 MANE Select	c.285A>G	p.Arg95Arg	synonymous	Exon 3 of 3	ENSP00000264376.4	P07320
ENSG00000295187	ENST00000728538.1		n.100+2688T>C		intron	N/A
ENSG00000295187	ENST00000728539.1		n.117+2688T>C		intron	N/A

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 4 multiple types (2)

not provided (2)

Aculeiform cataract (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over