2-208124445-G-A

Position:

chr2-208124445-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006891.4(CRYGD):c.9+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,582,836 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 9 hom., cov: 33)

Exomes 𝑓: 0.015 ( 195 hom. )

Consequence

CRYGD
NM_006891.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.69

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-208124445-G-A is Benign according to our data. Variant chr2-208124445-G-A is described in ClinVar as [Benign]. Clinvar id is 260063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0111 (1698/152306) while in subpopulation NFE AF= 0.0173 (1176/68012). AF 95% confidence interval is 0.0165. There are 9 homozygotes in gnomad4. There are 780 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1698 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYGD	NM_006891.4 linkuse as main transcript	c.9+20C>T		intron_variant		ENST00000264376.5	NP_008822.2	P07320A0A140CTX7
LOC100507443	NR_038437.1 linkuse as main transcript	n.97+5220G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGD	ENST00000264376.5 linkuse as main transcript	c.9+20C>T		intron_variant		1	NM_006891.4	ENSP00000264376.4		P07320

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1697

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00297

Gnomad AMI

AF:

0.0769

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.0116

AC:

2206

AN:

190104

Hom.:

AF XY:

0.0119

AC XY:

1222

AN XY:

102744

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00791

Gnomad ASJ exome

AF:

0.0262

Gnomad EAS exome

AF:

0.0000685

Gnomad SAS exome

AF:

0.00328

Gnomad FIN exome

AF:

0.00717

Gnomad NFE exome

AF:

0.0178

Gnomad OTH exome

AF:

0.0177

GnomAD4 exome

AF:

0.0148

AC:

21183

AN:

1430530

Hom.:

195

Cov.:

AF XY:

0.0144

AC XY:

10214

AN XY:

708586

show subpopulations

Gnomad4 AFR exome

AF:

0.00226

Gnomad4 AMR exome

AF:

0.00891

Gnomad4 ASJ exome

AF:

0.0239

Gnomad4 EAS exome

AF:

0.0000520

Gnomad4 SAS exome

AF:

0.00331

Gnomad4 FIN exome

AF:

0.00731

Gnomad4 NFE exome

AF:

0.0169

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.0111

AC:

1698

AN:

152306

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

780

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00296

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.0173

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00991

Hom.:

Bravo

AF:

0.0118

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Aculeiform cataract

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.3

DANN

Benign

0.87

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

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