2-208145688-CAA-C

Position:

• chr2-208145688-CAA-C

Variant summary

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

The NM_005210.4(CRYGB):​c.252+84_252+85delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,170,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 22)
  • Exomes 𝑓: 0.060 (0 hom.)
• Consequence: CRYGB NM_005210.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.14

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-CAA-C is Benign according to our data. Variant chr2-208145688-CAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1317988.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYGB	NM_005210.4	c.252+84_252+85delTT		intron_variant		ENST00000260988.5	NP_005201.2
CRYGB	XM_017003402.2	c.258+78_258+79delTT		intron_variant			XP_016858891.1
LOC100507443	NR_038437.1	n.221+8531_221+8532delAA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGB	ENST00000260988.5	c.252+84_252+85delTT		intron_variant		1	NM_005210.4	ENSP00000260988.4

Frequencies

GnomAD3 genomes AF: 0.00311 AC: 166 AN: 53446 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00943

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000521

Gnomad OTH AF: 0.00149

GnomAD4 exome AF: 0.0596 AC: 66545 AN: 1117364 Hom.: 0 AF XY: 0.0599 AC XY: 32644 AN XY: 544926

Gnomad4 AFR exome AF: 0.0752

Gnomad4 AMR exome AF: 0.0660

Gnomad4 ASJ exome AF: 0.0800

Gnomad4 EAS exome AF: 0.0693

Gnomad4 SAS exome AF: 0.0669

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.0566

Gnomad4 OTH exome AF: 0.0668

GnomAD4 genome AF: 0.00311 AC: 166 AN: 53438 Hom.: 0 Cov.: 22 AF XY: 0.00321 AC XY: 80 AN XY: 24902

Gnomad4 AFR AF: 0.00942

Gnomad4 AMR AF: 0.00264

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000521

Gnomad4 OTH AF: 0.00148

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 26, 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;