chrX-151739641-C-G

Position:

• chrX-151739641-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005140.3(CNGA2):​c.283C>G​(p.Leu95Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,098,166 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: 0.0000018 (0 hom. 1 hem.)
• Consequence: CNGA2 NM_005140.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2245534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA2	NM_005140.3	c.283C>G	p.Leu95Val	missense_variant	4/7	ENST00000329903.5	NP_005131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGA2	ENST00000329903.5	c.283C>G	p.Leu95Val	missense_variant	4/7	5	NM_005140.3	ENSP00000328478.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098166 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363520

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

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

Dec 05, 2022

The c.283C>G (p.L95V) alteration is located in exon 4 (coding exon 3) of the CNGA2 gene. This alteration results from a C to G substitution at nucleotide position 283, causing the leucine (L) at amino acid position 95 to be replaced by a valine (V). 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Uncertain	0.015	D
Sift4G	Benign	0.12	T
Polyphen		0.19	B
Vest4		0.38
MutPred		0.18		Gain of methylation at R99 (P = 0.1426);
MVP		0.57
MPC		0.15
ClinPred		0.92	D
GERP RS		5.6
Varity_R		0.29
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-150908113;