rs2242073

chr2-208129321-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020989.4(CRYGC):c.252+120A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,385,542 control chromosomes in the GnomAD database, including 17,637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2690 hom., cov: 33)
  • Exomes 𝑓: 0.15 (14947 hom.)
• Consequence: CRYGC NM_020989.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.353

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]

LOC100507443 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-208129321-T-G is Benign according to our data. Variant chr2-208129321-T-G is described in ClinVar as [Benign]. Clinvar id is 1262083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYGC	NM_020989.4	c.252+120A>C		intron_variant		ENST00000282141.4
LOC100507443	NR_038437.1	n.98-7735T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYGC	ENST00000282141.4	c.252+120A>C		intron_variant		1	NM_020989.4	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27462 AN: 152084 Hom.: 2665 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.0744

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.152 AC: 187219 AN: 1233340 Hom.: 14947 AF XY: 0.149 AC XY: 91286 AN XY: 611448

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.194

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.0458

Gnomad4 SAS exome AF: 0.0745

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.181 AC: 27539 AN: 152202 Hom.: 2690 Cov.: 33 AF XY: 0.179 AC XY: 13290 AN XY: 74402

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0535

Gnomad4 SAS AF: 0.0746

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.160

Alfa AF: 0.160 Hom.: 3265

Bravo AF: 0.188

Asia WGS AF: 0.0660 AC: 230 AN: 3478

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

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.4
Dann	Benign	0.33

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: rs2242073; hg19: chr2-208994045;