rs2305429

Variant names:

• chr2-208121661-A-G
• rs2305429
• NM_006891.4:c.*12T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-208121661-A-G
• chr2-208121661-A-C
• chr2-208121661-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006891.4(CRYGD):​c.*12T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,611,340 control chromosomes in the GnomAD database, including 693,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (63886 hom., cov: 32)
  • Exomes 𝑓: 0.93 (629838 hom.)
• Consequence: CRYGD NM_006891.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.256
• Publications: 18 publications found

Genes affected

CRYGD (HGNC:2411): (crystallin gamma D) Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Gamma-crystallins are a homogeneous group of highly symmetrical, monomeric proteins typically lacking connecting peptides and terminal extensions. They are differentially regulated after early development. Four gamma-crystallin genes (gamma-A through gamma-D) and three pseudogenes (gamma-E, gamma-F, gamma-G) are tandemly organized in a genomic segment as a gene cluster. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation. [provided by RefSeq, Jul 2008]

CRYGD Gene-Disease associations (from GenCC):

• cataract 4 multiple types

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

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

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

  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=-0.92).
• BP6: Variant 2-208121661-A-G is Benign according to our data. Variant chr2-208121661-A-G is described in ClinVar as Benign. ClinVar VariationId is 260059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006891.4. 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
	CRYGD	NM_006891.4	MANE Select	c.*12T>C		3_prime_UTR	Exon 3 of 3	NP_008822.2
	LOC100507443	NR_038437.1		n.97+2436A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYGD	ENST00000264376.5	TSL:1 MANE Select	c.*12T>C		3_prime_UTR	Exon 3 of 3	ENSP00000264376.4	P07320
	ENSG00000295187	ENST00000728538.1		n.100+2436A>G		intron	N/A
	ENSG00000295187	ENST00000728539.1		n.117+2436A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138812 AN: 152122 Hom.: 63830 Cov.: 32

Gnomad AFR AF: 0.919

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.900

GnomAD2 exomes AF: 0.877 AC: 218860 AN: 249596 AF XY: 0.880

Gnomad AFR exome AF: 0.915

Gnomad AMR exome AF: 0.777

Gnomad ASJ exome AF: 0.922

Gnomad EAS exome AF: 0.578

Gnomad FIN exome AF: 0.954

Gnomad NFE exome AF: 0.947

Gnomad OTH exome AF: 0.902

GnomAD4 exome AF: 0.926 AC: 1350908 AN: 1459100 Hom.: 629838 Cov.: 47 AF XY: 0.924 AC XY: 670029 AN XY: 725460

African (AFR) AF: 0.917 AC: 30613 AN: 33384

American (AMR) AF: 0.786 AC: 34919 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 23991 AN: 26074

East Asian (EAS) AF: 0.557 AC: 22066 AN: 39644

South Asian (SAS) AF: 0.824 AC: 70787 AN: 85938

European-Finnish (FIN) AF: 0.953 AC: 50743 AN: 53238

Middle Eastern (MID) AF: 0.876 AC: 5043 AN: 5754

European-Non Finnish (NFE) AF: 0.953 AC: 1058033 AN: 1110360

Other (OTH) AF: 0.908 AC: 54713 AN: 60256

GnomAD4 genome AF: 0.913 AC: 138930 AN: 152240 Hom.: 63886 Cov.: 32 AF XY: 0.908 AC XY: 67548 AN XY: 74410

African (AFR) AF: 0.919 AC: 38183 AN: 41544

American (AMR) AF: 0.838 AC: 12823 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3183 AN: 3468

East Asian (EAS) AF: 0.591 AC: 3050 AN: 5164

South Asian (SAS) AF: 0.799 AC: 3851 AN: 4818

European-Finnish (FIN) AF: 0.954 AC: 10109 AN: 10598

Middle Eastern (MID) AF: 0.856 AC: 250 AN: 292

European-Non Finnish (NFE) AF: 0.951 AC: 64673 AN: 68034

Other (OTH) AF: 0.897 AC: 1896 AN: 2114

Alfa AF: 0.933 Hom.: 81065

Bravo AF: 0.905

Asia WGS AF: 0.668 AC: 2323 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Cataract 4 multiple types (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.57
PhyloP100		-0.26
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: rs2305429; hg19: chr2-208986385;