Variant 2-208128311-GTAGTTG-TCTACGAGGGTATTGCCCCGTCTACGAGGTATTGCCCGTCTACGAGGGTATTGCCCCGTCTACGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_020989.4(CRYGC):c.411_417delCAACTACinsTCGTAGACGGGGCAATACCCTCGTAGACGGGCAATACCTCGTAGACGGGGCAATACCCTCGTAGA(p.Asn138ArgfsTer21) variant causes a frameshift, stop gained, missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CRYGC
NM_020989.4 frameshift, stop_gained, missense

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.18

Variant links:

Genes affected

CRYGC (HGNC:2410): (crystallin gamma C) This gene encodes a member of the beta/gamma-crystallin family of proteins. Crystallins constitute the major proteins of vertebrate eye lens and maintain the transparency and refractive index of the lens. This gene and several family members are present in a gene cluster on chromosome 2. Mutations in this gene have been shown to cause multiple types of cataract, including Coppock-like cataract and zonular pulverulent cataract, among others. [provided by RefSeq, Jan 2015]

CRYGC links:

LOC100507443 (HGNC:):

LOC100507443 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-208128311-GTAGTTG-TCTACGAGGGTATTGCCCCGTCTACGAGGTATTGCCCGTCTACGAGGGTATTGCCCCGTCTACGA is Pathogenic according to our data. Variant chr2-208128311-GTAGTTG-TCTACGAGGGTATTGCCCCGTCTACGAGGTATTGCCCGTCTACGAGGGTATTGCCCCGTCTACGA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2031157.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYGC	NM_020989.4 link	c.411_417delCAACTACinsTCGTAGACGGGGCAATACCCTCGTAGACGGGCAATACCTCGTAGACGGGGCAATACCCTCGTAGA	p.Asn138ArgfsTer21	frameshift_variant, stop_gained, missense_variant	Exon 3 of 3	ENST00000282141.4	NP_066269.1	P07315A0A0X8GLL6
LOC100507443	NR_038437.1 link	n.98-8745_98-8739delGTAGTTGinsTCTACGAGGGTATTGCCCCGTCTACGAGGTATTGCCCGTCTACGAGGGTATTGCCCCGTCTACGA		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYGC	ENST00000282141.4 link	c.411_417delCAACTACinsTCGTAGACGGGGCAATACCCTCGTAGACGGGCAATACCTCGTAGACGGGGCAATACCCTCGTAGA	p.Asn138ArgfsTer21	frameshift_variant, stop_gained, missense_variant	Exon 3 of 3	1	NM_020989.4	ENSP00000282141.3		P07315

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nuclear pulverulent cataract

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 28, 2022

This premature translational stop signal has been observed in individual(s) with congenital cataracts (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn138Argfs*21) in the CRYGC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acid(s) of the CRYGC protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.