Variant X-151742637-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_005140.3(CNGA2):c.584G>A(p.Arg195His) variant causes a missense change. The variant allele was found at a frequency of 0.000111 in 1,192,254 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., 2 hem., cov: 20)

Exomes 𝑓: 0.00012 ( 0 hom. 39 hem. )

Consequence

CNGA2
NM_005140.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.55

Variant links:

Genes affected

CNGA2 (HGNC:2149): (cyclic nucleotide gated channel subunit alpha 2) The protein encoded by this gene represents the alpha subunit of a cyclic nucleotide-gated olfactory channel. The encoded protein contains a carboxy-terminal leucine zipper that mediates channel formation. [provided by RefSeq, Jan 2010]

CNGA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36526296).

BP6

Variant X-151742637-G-A is Benign according to our data. Variant chrX-151742637-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661651.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA2	NM_005140.3 linkuse as main transcript	c.584G>A	p.Arg195His	missense_variant	6/7	ENST00000329903.5	NP_005131.1	Q16280B3KXY3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGA2	ENST00000329903.5 linkuse as main transcript	c.584G>A	p.Arg195His	missense_variant	6/7	5	NM_005140.3	ENSP00000328478.4		Q16280

Frequencies

GnomAD3 genomes

AF:

0.0000456

AC:

AN:

109711

Hom.:

Cov.:

AF XY:

0.0000626

AC XY:

AN XY:

31959

show subpopulations

Gnomad AFR

AF:

0.0000669

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000395

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000378

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000395

AC:

AN:

177155

Hom.:

AF XY:

0.0000323

AC XY:

AN XY:

61957

show subpopulations

Gnomad AFR exome

AF:

0.0000779

Gnomad AMR exome

AF:

0.0000379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000629

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000117

AC:

127

AN:

1082543

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

348907

show subpopulations

Gnomad4 AFR exome

AF:

0.000192

Gnomad4 AMR exome

AF:

0.0000578

Gnomad4 ASJ exome

AF:

0.0000523

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000190

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000138

Gnomad4 OTH exome

AF:

0.0000659

GnomAD4 genome

AF:

0.0000456

AC:

AN:

109711

Hom.:

Cov.:

AF XY:

0.0000626

AC XY:

AN XY:

31959

show subpopulations

Gnomad4 AFR

AF:

0.0000669

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000395

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 07, 2024

The c.584G>A (p.R195H) alteration is located in exon 6 (coding exon 5) of the CNGA2 gene. This alteration results from a G to A substitution at nucleotide position 584, causing the arginine (R) at amino acid position 195 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

CNGA2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Pathogenic

0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.37

MetaSVM

Uncertain

0.78

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-4.3

REVEL

Pathogenic

0.74

Sift

Benign

0.28

Sift4G

Benign

0.18

Polyphen

0.029

Vest4

0.28

MVP

0.88

MPC

0.092

ClinPred

0.11

GERP RS

5.6

Varity_R

0.43

gMVP

0.76

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over