X-151743137-C-G

Variant names:

• chrX-151743137-C-G
• rs1057519072
• NM_005140.3:c.634C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005140.3(CNGA2):​c.634C>G​(p.Arg212Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,091,605 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R212Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 17)
  • Exomes 𝑓: 0.0000027 (0 hom. 2 hem.)
• Consequence: CNGA2 NM_005140.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 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>G	p.Arg212Gly	missense	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>G	p.Arg212Gly	missense	Exon 7 of 7	ENSP00000328478.4	Q16280

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome AF: 0.00000275 AC: 3 AN: 1091605 Hom.: 0 Cov.: 31 AF XY: 0.00000559 AC XY: 2 AN XY: 357969

African (AFR) AF: 0.00 AC: 0 AN: 26320

American (AMR) AF: 0.00 AC: 0 AN: 35017

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19228

East Asian (EAS) AF: 0.00 AC: 0 AN: 30053

South Asian (SAS) AF: 0.00 AC: 0 AN: 53702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4104

European-Non Finnish (NFE) AF: 0.00000358 AC: 3 AN: 836960

Other (OTH) AF: 0.00 AC: 0 AN: 45783

GnomAD4 genome Cov.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Uncertain	0.77	D
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.8	D
REVEL	Pathogenic	0.68
Sift	Benign	0.19	T
Sift4G	Benign	0.24	T
Polyphen		0.031	B
Vest4		0.45
MutPred		0.61		Loss of methylation at R212 (P = 0.0323)
MVP		0.93
MPC		0.10
ClinPred		0.81	D
GERP RS		3.5
Varity_R		0.52
gMVP		0.91
Mutation Taster		=83/17	polymorphism

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: rs1057519072; hg19: chrX-150911609;