2-208145688-C-CA

Position:

• chr2-208145688-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005210.4(CRYGB):​c.252+85dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 52,436 control chromosomes in the GnomAD database, including 73 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.051 (73 hom., cov: 22)
  • Exomes 𝑓: 0.091 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRYGB NM_005210.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.489

Genes affected

CRYGB (HGNC:2409): (crystallin gamma B) 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 -10 ACMG points.

• BP6: Variant 2-208145688-C-CA is Benign according to our data. Variant chr2-208145688-C-CA is described in ClinVar as [Benign]. Clinvar id is 1263173.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYGB	NM_005210.4	c.252+85dupT		intron_variant		ENST00000260988.5	NP_005201.2
CRYGB	XM_017003402.2	c.258+79dupT		intron_variant			XP_016858891.1
LOC100507443	NR_038437.1	n.221+8532dupA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGB	ENST00000260988.5	c.252+85dupT		intron_variant		1	NM_005210.4	ENSP00000260988.4

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 2676 AN: 52444 Hom.: 73 Cov.: 22

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.0203

Gnomad EAS AF: 0.0868

Gnomad SAS AF: 0.00832

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0109

Gnomad NFE AF: 0.0505

Gnomad OTH AF: 0.0514

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0908 AC: 108177 AN: 1191546 Hom.: 1 AF XY: 0.0890 AC XY: 51795 AN XY: 581688

Gnomad4 AFR exome AF: 0.0852

Gnomad4 AMR exome AF: 0.0479

Gnomad4 ASJ exome AF: 0.0786

Gnomad4 EAS exome AF: 0.0933

Gnomad4 SAS exome AF: 0.0774

Gnomad4 FIN exome AF: 0.0703

Gnomad4 NFE exome AF: 0.0938

Gnomad4 OTH exome AF: 0.0903

GnomAD4 genome AF: 0.0510 AC: 2675 AN: 52436 Hom.: 73 Cov.: 22 AF XY: 0.0491 AC XY: 1203 AN XY: 24504

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.0203

Gnomad4 EAS AF: 0.0870

Gnomad4 SAS AF: 0.00839

Gnomad4 FIN AF: 0.0300

Gnomad4 NFE AF: 0.0505

Gnomad4 OTH AF: 0.0524

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs554918356; hg19: chr2-209010412;