2-208124445-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006891.4(CRYGD):c.9+20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,582,832 control chromosomes in the GnomAD database, including 441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 215 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 226 hom. )

Consequence

CRYGD
NM_006891.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.69

Publications

1 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-208124445-G-C is Benign according to our data. Variant chr2-208124445-G-C is described in ClinVar as Benign. ClinVar VariationId is 1261000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0986 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.9+20C>G		intron	N/A	NP_008822.2
	LOC100507443	NR_038437.1		n.97+5220G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CRYGD	ENST00000264376.5	TSL:1 MANE Select	c.9+20C>G	intron	N/A	ENSP00000264376.4	P07320
ENSG00000295187	ENST00000728538.1		n.100+5220G>C	intron	N/A
ENSG00000295187	ENST00000728539.1		n.117+5220G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4425

AN:

152176

Hom.:

214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0143

GnomAD2 exomes

AF:

0.00713

AC:

1355

AN:

190104

AF XY:

0.00539

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000685

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000248

Gnomad OTH exome

AF:

0.00482

GnomAD4 exome

AF:

0.00310

AC:

4434

AN:

1430538

Hom.:

226

Cov.:

AF XY:

0.00272

AC XY:

1924

AN XY:

708596

show subpopulations

African (AFR)

AF:

0.108

AC:

3574

AN:

33146

American (AMR)

AF:

0.00524

AC:

203

AN:

38720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25404

East Asian (EAS)

AF:

0.0000520

AC:

AN:

38496

South Asian (SAS)

AF:

0.000146

AC:

AN:

82160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50220

Middle Eastern (MID)

AF:

0.00515

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.000201

AC:

221

AN:

1097458

Other (OTH)

AF:

0.00663

AC:

393

AN:

59298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

272

544

817

1089

1361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<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:

0.0292

AC:

4444

AN:

152294

Hom.:

215

Cov.:

AF XY:

0.0286

AC XY:

2132

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.101

AC:

4203

AN:

41552

American (AMR)

AF:

0.0119

AC:

182

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68012

Other (OTH)

AF:

0.0142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

202

404

607

809

1011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.00101

Hom.:

Bravo

AF:

0.0338

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Aculeiform cataract (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.93

(source)

DANN

Benign

0.65

PhyloP100

-1.7

PromoterAI

0.023

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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