2-98377846-T-G

Variant names:

• chr2-98377846-T-G
• rs58990587
• NM_001298.3:c.215+46T>G

Variant summary

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

The NM_001298.3(CNGA3):​c.215+46T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 1,542,422 control chromosomes in the GnomAD database, including 2,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (383 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2565 hom.)
• Consequence: CNGA3 NM_001298.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.969
• Publications: 4 publications found

Genes affected

CNGA3 (HGNC:2150): (cyclic nucleotide gated channel subunit alpha 3) This gene encodes a member of the cyclic nucleotide-gated cation channel protein family which is required for normal vision and olfactory signal transduction. Mutations in this gene are associated with achromatopsia (rod monochromacy) and color blindness. Two alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

CNGA3 Gene-Disease associations (from GenCC):

• achromatopsia 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia
• CNGA3-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• achromatopsia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-98377846-T-G is Benign according to our data. Variant chr2-98377846-T-G is described in CliVar as Benign. Clinvar id is 257963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-98377846-T-G is described in CliVar as Benign. Clinvar id is 257963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-98377846-T-G is described in CliVar as Benign. Clinvar id is 257963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-98377846-T-G is described in CliVar as Benign. Clinvar id is 257963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-98377846-T-G is described in CliVar as Benign. Clinvar id is 257963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-98377846-T-G is described in CliVar as Benign. Clinvar id is 257963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-98377846-T-G is described in CliVar as Benign. Clinvar id is 257963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGA3	NM_001298.3	c.215+46T>G		intron_variant	Intron 3 of 7	ENST00000272602.7	NP_001289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGA3	ENST00000272602.7	c.215+46T>G		intron_variant	Intron 3 of 7	1	NM_001298.3	ENSP00000272602.2
CNGA3	ENST00000436404.6	c.215+46T>G		intron_variant	Intron 3 of 6	1		ENSP00000410070.2
CNGA3	ENST00000409937.1	n.203+46T>G		intron_variant	Intron 2 of 7	2

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9708 AN: 152088 Hom.: 380 Cov.: 32

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0389

Gnomad FIN AF: 0.0371

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.0655

GnomAD2 exomes AF: 0.0497 AC: 9234 AN: 185940 AF XY: 0.0493

Gnomad AFR exome AF: 0.0957

Gnomad AMR exome AF: 0.0329

Gnomad ASJ exome AF: 0.0331

Gnomad EAS exome AF: 0.00290

Gnomad FIN exome AF: 0.0328

Gnomad NFE exome AF: 0.0643

Gnomad OTH exome AF: 0.0542

GnomAD4 exome AF: 0.0577 AC: 80159 AN: 1390216 Hom.: 2565 Cov.: 22 AF XY: 0.0571 AC XY: 39382 AN XY: 689150

African (AFR) AF: 0.0911 AC: 2910 AN: 31946

American (AMR) AF: 0.0334 AC: 1301 AN: 38974

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 835 AN: 24532

East Asian (EAS) AF: 0.00128 AC: 49 AN: 38260

South Asian (SAS) AF: 0.0436 AC: 3490 AN: 80134

European-Finnish (FIN) AF: 0.0360 AC: 1827 AN: 50704

Middle Eastern (MID) AF: 0.0630 AC: 265 AN: 4208

European-Non Finnish (NFE) AF: 0.0624 AC: 66337 AN: 1063820

Other (OTH) AF: 0.0546 AC: 3145 AN: 57638

GnomAD4 genome AF: 0.0640 AC: 9735 AN: 152206 Hom.: 383 Cov.: 32 AF XY: 0.0617 AC XY: 4596 AN XY: 74434

African (AFR) AF: 0.0922 AC: 3827 AN: 41526

American (AMR) AF: 0.0469 AC: 717 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5178

South Asian (SAS) AF: 0.0392 AC: 189 AN: 4826

European-Finnish (FIN) AF: 0.0371 AC: 393 AN: 10596

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0626 AC: 4260 AN: 67998

Other (OTH) AF: 0.0648 AC: 137 AN: 2114

Alfa AF: 0.0493 Hom.: 107

Bravo AF: 0.0672

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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	-0.92
CADD	Benign	7.6
DANN	Benign	0.37
PhyloP100		0.97
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: rs58990587; hg19: chr2-98994309;