rs864309689

Variant names:

• chr2-208128399-GG-A
• rs864309689
• NM_020989.4:c.328_329delCCinsT
• CRYGC p.Pro110SerfsTer37

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_020989.4(CRYGC):​c.328_329delCCinsT​(p.Pro110SerfsTer37) variant causes a frameshift, missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRYGC NM_020989.4 frameshift, missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.09
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• cataract 2, multiple types

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• cataract - microcornea syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset lamellar cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pulverulent cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000295187 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 11 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 22 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-208128399-GG-A is Pathogenic according to our data. Variant chr2-208128399-GG-A is described in ClinVar as Pathogenic. ClinVar VariationId is 217337.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020989.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYGC	NM_020989.4	MANE Select	c.328_329delCCinsT	p.Pro110SerfsTer37	frameshift missense	Exon 3 of 3	NP_066269.1	P07315
	LOC100507443	NR_038437.1		n.98-8657_98-8656delGGinsA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYGC	ENST00000282141.4	TSL:1 MANE Select	c.328_329delCCinsT	p.Pro110SerfsTer37	frameshift missense	Exon 3 of 3	ENSP00000282141.3	P07315
	ENSG00000295187	ENST00000728538.1		n.101-8657_101-8656delGGinsA		intron	N/A
	ENSG00000295187	ENST00000728539.1		n.118-8657_118-8656delGGinsA		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Developmental cataract (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.1
Mutation Taster		=11/189	disease causing

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs864309689;

hg19: chr2-208993123;