2-98377671-A-G

Variant names:

• chr2-98377671-A-G
• rs2279859
• NM_001298.3:c.102-16A>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.102-16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 1,607,010 control chromosomes in the GnomAD database, including 6,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (566 hom., cov: 33)
  • Exomes 𝑓: 0.085 (5633 hom.)
• Consequence: CNGA3 NM_001298.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.592
• Publications: 5 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: Illumina, G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.8).
• BP6: Variant 2-98377671-A-G is Benign according to our data. Variant chr2-98377671-A-G is described in ClinVar as Benign. ClinVar VariationId is 257961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001298.3. 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
	CNGA3	NM_001298.3	MANE Select	c.102-16A>G		intron	N/A	NP_001289.1	Q16281-1
	CNGA3	NM_001079878.2		c.102-16A>G		intron	N/A	NP_001073347.1	Q16281-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA3	ENST00000272602.7	TSL:1 MANE Select	c.102-16A>G		intron	N/A	ENSP00000272602.2	Q16281-1
	CNGA3	ENST00000436404.6	TSL:1	c.102-16A>G		intron	N/A	ENSP00000410070.2	Q16281-2
	CNGA3	ENST00000853268.1		c.102-16A>G		intron	N/A	ENSP00000523327.1

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12026 AN: 152110 Hom.: 565 Cov.: 33

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0898

Gnomad OTH AF: 0.0880

GnomAD2 exomes AF: 0.0828 AC: 20163 AN: 243392 AF XY: 0.0841

Gnomad AFR exome AF: 0.0465

Gnomad AMR exome AF: 0.0489

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.146

Gnomad FIN exome AF: 0.0744

Gnomad NFE exome AF: 0.0879

Gnomad OTH exome AF: 0.0955

GnomAD4 exome AF: 0.0852 AC: 123923 AN: 1454782 Hom.: 5633 Cov.: 30 AF XY: 0.0852 AC XY: 61647 AN XY: 723200

African (AFR) AF: 0.0464 AC: 1549 AN: 33354

American (AMR) AF: 0.0514 AC: 2278 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 4036 AN: 26006

East Asian (EAS) AF: 0.144 AC: 5688 AN: 39570

South Asian (SAS) AF: 0.0612 AC: 5195 AN: 84908

European-Finnish (FIN) AF: 0.0716 AC: 3797 AN: 53032

Middle Eastern (MID) AF: 0.156 AC: 801 AN: 5140

European-Non Finnish (NFE) AF: 0.0856 AC: 94921 AN: 1108356

Other (OTH) AF: 0.0942 AC: 5658 AN: 60080

GnomAD4 genome AF: 0.0791 AC: 12035 AN: 152228 Hom.: 566 Cov.: 33 AF XY: 0.0790 AC XY: 5875 AN XY: 74414

African (AFR) AF: 0.0495 AC: 2056 AN: 41546

American (AMR) AF: 0.0720 AC: 1101 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3470

East Asian (EAS) AF: 0.139 AC: 720 AN: 5178

South Asian (SAS) AF: 0.0545 AC: 263 AN: 4824

European-Finnish (FIN) AF: 0.0748 AC: 792 AN: 10592

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0898 AC: 6106 AN: 68010

Other (OTH) AF: 0.0885 AC: 187 AN: 2114

Alfa AF: 0.0772 Hom.: 381

Bravo AF: 0.0797

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Achromatopsia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.66
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs2279859; hg19: chr2-98994134;