chr2-208121661-A-G

Position:

chr2-208121661-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006891.4(CRYGD):c.*12T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,611,340 control chromosomes in the GnomAD database, including 693,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.91 ( 63886 hom., cov: 32)

Exomes 𝑓: 0.93 ( 629838 hom. )

Consequence

CRYGD
NM_006891.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.256

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=-0.92).

BP6

Variant 2-208121661-A-G is Benign according to our data. Variant chr2-208121661-A-G is described in ClinVar as [Benign]. Clinvar id is 260059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-208121661-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYGD	NM_006891.4 link	c.*12T>C		3_prime_UTR_variant	3/3	ENST00000264376.5	NP_008822.2	P07320A0A140CTX7
LOC100507443	NR_038437.1 link	n.97+2436A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGD	ENST00000264376 link	c.*12T>C		3_prime_UTR_variant	3/3	1	NM_006891.4	ENSP00000264376.4		P07320

Frequencies

GnomAD3 genomes

AF:

0.913

AC:

138812

AN:

152122

Hom.:

63830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.919

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.838

Gnomad ASJ

AF:

0.918

Gnomad EAS

AF:

0.590

Gnomad SAS

AF:

0.798

Gnomad FIN

AF:

0.954

Gnomad MID

AF:

0.850

Gnomad NFE

AF:

0.951

Gnomad OTH

AF:

0.900

GnomAD3 exomes

AF:

0.877

AC:

218860

AN:

249596

Hom.:

97501

AF XY:

0.880

AC XY:

118893

AN XY:

135088

show subpopulations

Gnomad AFR exome

AF:

0.915

Gnomad AMR exome

AF:

0.777

Gnomad ASJ exome

AF:

0.922

Gnomad EAS exome

AF:

0.578

Gnomad SAS exome

AF:

0.815

Gnomad FIN exome

AF:

0.954

Gnomad NFE exome

AF:

0.947

Gnomad OTH exome

AF:

0.902

GnomAD4 exome

AF:

0.926

AC:

1350908

AN:

1459100

Hom.:

629838

Cov.:

AF XY:

0.924

AC XY:

670029

AN XY:

725460

show subpopulations

Gnomad4 AFR exome

AF:

0.917

Gnomad4 AMR exome

AF:

0.786

Gnomad4 ASJ exome

AF:

0.920

Gnomad4 EAS exome

AF:

0.557

Gnomad4 SAS exome

AF:

0.824

Gnomad4 FIN exome

AF:

0.953

Gnomad4 NFE exome

AF:

0.953

Gnomad4 OTH exome

AF:

0.908

GnomAD4 genome

AF:

0.913

AC:

138930

AN:

152240

Hom.:

63886

Cov.:

AF XY:

0.908

AC XY:

67548

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.919

Gnomad4 AMR

AF:

0.838

Gnomad4 ASJ

AF:

0.918

Gnomad4 EAS

AF:

0.591

Gnomad4 SAS

AF:

0.799

Gnomad4 FIN

AF:

0.954

Gnomad4 NFE

AF:

0.951

Gnomad4 OTH

AF:

0.897

Alfa

AF:

0.935

Hom.:

61857

Bravo

AF:

0.905

Asia WGS

AF:

0.668

AC:

2323

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 4 multiple types

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.5

DANN

Benign

0.57

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