chr7-144259474-G-C

Position:

• chr7-144259474-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005328.2(OR2A7):​c.155C>G​(p.Ser52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A7 NM_001005328.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0320

Genes affected

OR2A7 (HGNC:8234): (olfactory receptor family 2 subfamily A member 7) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ARHGEF34P (HGNC:):

ARHGEF35-AS1 (HGNC:41292): (ARHGEF35 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062807202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2A7	NM_001005328.2	c.155C>G	p.Ser52Cys	missense_variant	2/2	ENST00000641841.1
ARHGEF34P	NR_033942.1	n.3726C>G		non_coding_transcript_exon_variant	13/13
ARHGEF35-AS1	NR_126022.1	n.494-20998G>C		intron_variant, non_coding_transcript_variant
OR2A1-AS1	NR_126023.1	n.608-19731C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2A7	ENST00000641841.1	c.155C>G	p.Ser52Cys	missense_variant	2/2		NM_001005328.2	P1
ARHGEF35-AS1	ENST00000460955.5	n.494-20998G>C		intron_variant, non_coding_transcript_variant		4
OR2A7	ENST00000493325.1	c.155C>G	p.Ser52Cys	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.000380 AC: 52 AN: 136740 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.000111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000829

Gnomad ASJ AF: 0.00469

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000243

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0113

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00165

GnomAD3 exomes AF: 0.000346 AC: 85 AN: 245476 Hom.: 0 AF XY: 0.000367 AC XY: 49 AN XY: 133640

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000383

Gnomad ASJ exome AF: 0.00445

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000162

Gnomad OTH exome AF: 0.000835

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000210 AC: 300 AN: 1430366 Hom.: 0 Cov.: 30 AF XY: 0.000219 AC XY: 156 AN XY: 713148

Gnomad4 AFR exome AF: 0.000123

Gnomad4 AMR exome AF: 0.000431

Gnomad4 ASJ exome AF: 0.00352

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000199

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000118

Gnomad4 OTH exome AF: 0.000407

GnomAD4 genome AF: 0.000380 AC: 52 AN: 136818 Hom.: 0 Cov.: 20 AF XY: 0.000454 AC XY: 30 AN XY: 66014

Gnomad4 AFR AF: 0.000111

Gnomad4 AMR AF: 0.000828

Gnomad4 ASJ AF: 0.00469

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000244

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000236

Gnomad4 OTH AF: 0.00163

Alfa AF: 0.00277 Hom.: 0

ExAC AF: 0.000901 AC: 109

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

Jan 27, 2022

The c.155C>G (p.S52C) alteration is located in exon 1 (coding exon 1) of the OR2A7 gene. This alteration results from a C to G substitution at nucleotide position 155, causing the serine (S) at amino acid position 52 to be replaced by a cysteine (C). 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	0.076
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	17
DANN	Benign	0.74
DEOGEN2	Benign	0.0083	T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.037	N
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.0063	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.4	.;N
REVEL	Benign	0.022
Sift	Benign	0.20	.;T
Sift4G	Benign	0.12	.;T
Polyphen		0.0060	B;B
Vest4		0.14
MutPred		0.52		Loss of catalytic residue at S52 (P = 0.1789);Loss of catalytic residue at S52 (P = 0.1789);
MVP		0.22
ClinPred		0.0081	T
GERP RS		1.0
Varity_R		0.067
gMVP		0.12

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: rs776485163; hg19: chr7-143956567; COSMIC: COSV71827147; COSMIC: COSV71827147;