2-208129973-C-T

Variant names:

• chr2-208129973-C-T
• rs2242071
• ENST00000728538.1:n.101-7083C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000728538.1(ENSG00000295187):​n.101-7083C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 780,104 control chromosomes in the GnomAD database, including 204,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (39520 hom., cov: 32)
  • Exomes 𝑓: 0.72 (165464 hom.)
• Consequence: ENSG00000295187 ENST00000728538.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.628
• Publications: 4 publications found

Genes affected

ENSG00000295187 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 2-208129973-C-T is Benign according to our data. Variant chr2-208129973-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291617.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100507443	NR_038437.1	n.98-7083C>T		intron_variant	Intron 1 of 2
CRYGC	NM_020989.4	c.-181G>A		upstream_gene_variant		ENST00000282141.4	NP_066269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000295187	ENST00000728538.1	n.101-7083C>T		intron_variant	Intron 1 of 2
ENSG00000295187	ENST00000728539.1	n.118-7083C>T		intron_variant	Intron 1 of 2
CRYGC	ENST00000282141.4	c.-181G>A		upstream_gene_variant		1	NM_020989.4	ENSP00000282141.3

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109099 AN: 151982 Hom.: 39478 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.710

GnomAD4 exome AF: 0.721 AC: 452796 AN: 628004 Hom.: 165464 AF XY: 0.723 AC XY: 243845 AN XY: 337154

African (AFR) AF: 0.714 AC: 12096 AN: 16946

American (AMR) AF: 0.556 AC: 19056 AN: 34278

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 14098 AN: 19354

East Asian (EAS) AF: 0.505 AC: 17215 AN: 34058

South Asian (SAS) AF: 0.714 AC: 45588 AN: 63826

European-Finnish (FIN) AF: 0.753 AC: 27097 AN: 35992

Middle Eastern (MID) AF: 0.668 AC: 1813 AN: 2714

European-Non Finnish (NFE) AF: 0.753 AC: 292304 AN: 388034

Other (OTH) AF: 0.717 AC: 23529 AN: 32802

GnomAD4 genome AF: 0.718 AC: 109198 AN: 152100 Hom.: 39520 Cov.: 32 AF XY: 0.715 AC XY: 53176 AN XY: 74348

African (AFR) AF: 0.718 AC: 29781 AN: 41480

American (AMR) AF: 0.604 AC: 9237 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2490 AN: 3468

East Asian (EAS) AF: 0.536 AC: 2760 AN: 5152

South Asian (SAS) AF: 0.702 AC: 3384 AN: 4820

European-Finnish (FIN) AF: 0.755 AC: 7985 AN: 10578

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.752 AC: 51159 AN: 67990

Other (OTH) AF: 0.711 AC: 1505 AN: 2116

Alfa AF: 0.734 Hom.: 54535

Bravo AF: 0.705

Asia WGS AF: 0.607 AC: 2114 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 29, 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	-0.28
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		0.63
PromoterAI		-0.00020	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2242071; hg19: chr2-208994697; COSMIC: COSV56408336;