Variant 2-218993399-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_057093.2(CRYBA2):c.-223C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 549,804 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

CRYBA2
NM_057093.2 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.270

Variant links:

Genes affected

CRYBA2 (HGNC:2395): (crystallin beta A2) Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of the vertebrate eye, which function to maintain 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 defined 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. Beta-crystallins, the most heterogeneous, differ by the presence of the C-terminal extension (present in the basic group but absent in the acidic group). Beta-crystallins form aggregates of different sizes and are able to form homodimers through self-association or heterodimers with other beta-crystallins. This gene is a beta acidic group member. Three alternatively spliced transcript variants encoding identical proteins have been reported. [provided by RefSeq, Jul 2008]

CRYBA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 2-218993399-G-A is Benign according to our data. Variant chr2-218993399-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1316549.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBA2	NM_057093.2 linkuse as main transcript	c.-223C>T		5_prime_UTR_variant	1/4	ENST00000295728.7	NP_476434.1	P53672A0A024R429
CRYBA2	NM_057094.2 linkuse as main transcript	c.-29C>T		5_prime_UTR_variant	1/5		NP_476435.1	P53672A0A024R429

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRYBA2	ENST00000295728.7 linkuse as main transcript	c.-223C>T	5_prime_UTR_variant	1/4	1	NM_057093.2	ENSP00000295728.2	P53672
CRYBA2	ENST00000392096.6 linkuse as main transcript	c.-29C>T	5_prime_UTR_variant	1/5	1		ENSP00000375946.2	P53672
CRYBA2	ENST00000453769.1 linkuse as main transcript	c.-105C>T	5_prime_UTR_variant	1/4	3		ENSP00000395120.1	C9JDH2

Frequencies

GnomAD3 genomes

AF:

0.00356

AC:

542

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.00

Gnomad OTH

AF:

0.00287

GnomAD4 exome

AF:

0.000337

AC:

134

AN:

397482

Hom.:

Cov.:

AF XY:

0.000299

AC XY:

AN XY:

207640

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.000876

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000280

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000807

Gnomad4 OTH exome

AF:

0.000632

GnomAD4 genome

AF:

0.00355

AC:

541

AN:

152322

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

255

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00285

Hom.:

Bravo

AF:

0.00397

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.9

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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