X-151738556-A-G

Position:

• chrX-151738556-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005140.3(CNGA2):​c.73A>G​(p.Lys25Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,524 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 2 hem.)
• Consequence: CNGA2 NM_005140.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.94

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18461594).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA2	NM_005140.3	c.73A>G	p.Lys25Glu	missense_variant	2/7	ENST00000329903.5	NP_005131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGA2	ENST00000329903.5	c.73A>G	p.Lys25Glu	missense_variant	2/7	5	NM_005140.3	ENSP00000328478.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097524 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 2 AN XY: 362882

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000993

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.73A>G (p.K25E) alteration is located in exon 2 (coding exon 1) of the CNGA2 gene. This alteration results from a A to G substitution at nucleotide position 73, causing the lysine (K) at amino acid position 25 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.31	N
REVEL	Uncertain	0.39
Sift	Benign	0.20	T
Sift4G	Benign	0.27	T
Polyphen		0.093	B
Vest4		0.30
MutPred		0.26		Loss of ubiquitination at K25 (P = 9e-04);
MVP		0.84
MPC		0.12
ClinPred		0.49	T
GERP RS		4.8
Varity_R		0.19
gMVP		0.42

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

Other links and lift over

dbSNP: rs2015270933; hg19: chrX-150907028;