Genetic Variant CNGA2:p.Arg212Arg (chrX-151743137-C-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_005140.3(CNGA2):c.634C>A(p.Arg212Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000156 in 1,091,604 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 17)

Exomes 𝑓: 0.000016 ( 0 hom. 4 hem. )

Failed GnomAD Quality Control

Consequence

CNGA2
NM_005140.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

isolated congenital anosmia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
anosmia
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

CNGA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=1.51 with no splicing effect.

BS2

High AC in GnomAdExome4 at 17 AD,XL gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005140.3. 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
	CNGA2	NM_005140.3	MANE Select	c.634C>A	p.Arg212Arg	synonymous	Exon 7 of 7	NP_005131.1	Q16280

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA2	ENST00000329903.5	TSL:5 MANE Select	c.634C>A	p.Arg212Arg	synonymous	Exon 7 of 7	ENSP00000328478.4	Q16280

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

98093

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000552

AC:

AN:

181142

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000156

AC:

AN:

1091604

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

357968

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26320

American (AMR)

AF:

0.00

AC:

AN:

35017

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19228

East Asian (EAS)

AF:

0.00

AC:

AN:

30053

South Asian (SAS)

AF:

0.00

AC:

AN:

53702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4104

European-Non Finnish (NFE)

AF:

0.0000203

AC:

AN:

836959

Other (OTH)

AF:

0.00

AC:

AN:

45783

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

98093

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

22383

African (AFR)

AF:

0.00

AC:

AN:

26255

American (AMR)

AF:

0.00

AC:

AN:

8671

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2465

East Asian (EAS)

AF:

0.00

AC:

AN:

3147

South Asian (SAS)

AF:

0.00

AC:

AN:

1927

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4215

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

49305

Other (OTH)

AF:

0.00

AC:

AN:

1273

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

7.8

(source)

DANN

Benign

0.56

PhyloP100

1.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over