rs113206037

chr2-208124445-G-Achr2-208124445-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.69

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]

LOC100507443 (HGNC:):

ACMG classification

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 GnomAd at 1697 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYGD	NM_006891.4	c.9+20C>T		intron_variant		ENST00000264376.5
LOC100507443	NR_038437.1	n.97+5220G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYGD	ENST00000264376.5	c.9+20C>T		intron_variant		1	NM_006891.4	P1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1697 AN: 152188 Hom.: 9 Cov.: 33

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.: 25 AF XY: 0.0119 AC XY: 1222 AN XY: 102744

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.: 35 AF XY: 0.0144 AC XY: 10214 AN XY: 708586

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.: 9 Cov.: 33 AF XY: 0.0105 AC XY: 780 AN XY: 74486

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.: 4

Bravo AF: 0.0118

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Aculeiform cataract Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 11, 2023

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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

Other links and lift over

dbSNP: rs113206037; hg19: chr2-208989169; COSMIC: COSV52205477; COSMIC: COSV52205477;