2-208129321-T-G

Variant names:

• chr2-208129321-T-G
• rs2242073
• NM_020989.4:c.252+120A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.353
• Publications: 16 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: Benign. The variant received -20 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 VariationId is 1262083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CRYGC	NM_020989.4	c.252+120A>C		intron_variant	Intron 2 of 2	ENST00000282141.4	NP_066269.1
LOC100507443	NR_038437.1	n.98-7735T>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYGC	ENST00000282141.4	c.252+120A>C		intron_variant	Intron 2 of 2	1	NM_020989.4	ENSP00000282141.3
ENSG00000295187	ENST00000728538.1	n.101-7735T>G		intron_variant	Intron 1 of 2
ENSG00000295187	ENST00000728539.1	n.118-7735T>G		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.242 AC: 6708 AN: 27740

American (AMR) AF: 0.194 AC: 6421 AN: 33164

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 2917 AN: 20050

East Asian (EAS) AF: 0.0458 AC: 1751 AN: 38248

South Asian (SAS) AF: 0.0745 AC: 5131 AN: 68842

European-Finnish (FIN) AF: 0.161 AC: 7931 AN: 49240

Middle Eastern (MID) AF: 0.170 AC: 589 AN: 3464

European-Non Finnish (NFE) AF: 0.157 AC: 147884 AN: 940686

Other (OTH) AF: 0.152 AC: 7887 AN: 51906

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

African (AFR) AF: 0.242 AC: 10060 AN: 41522

American (AMR) AF: 0.195 AC: 2985 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3472

East Asian (EAS) AF: 0.0535 AC: 277 AN: 5182

South Asian (SAS) AF: 0.0746 AC: 360 AN: 4824

European-Finnish (FIN) AF: 0.160 AC: 1695 AN: 10594

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11067 AN: 68006

Other (OTH) AF: 0.160 AC: 337 AN: 2110

Alfa AF: 0.165 Hom.: 7306

Bravo AF: 0.188

Asia WGS AF: 0.0660 AC: 230 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.33
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2242073; hg19: chr2-208994045;