7-144232642-C-T

Variant names:

• chr7-144232642-C-T
• rs776548474
• NM_001001802.3:c.202G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_001001802.3(OR2A42):​c.202G>A​(p.Val68Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000074 (1 hom., cov: 15)
  • Exomes 𝑓: 0.000092 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A42 NM_001001802.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -4.56
• Publications: 4 publications found

Genes affected

OR2A42 (HGNC:31230): (olfactory receptor family 2 subfamily A member 42) 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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02929464).
• BP6: Variant 7-144232642-C-T is Benign according to our data. Variant chr7-144232642-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2658124.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001802.3. 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
	OR2A42	NM_001001802.3	MANE Select	c.202G>A	p.Val68Ile	missense	Exon 3 of 3	NP_001001802.2
	ARHGEF35-AS1	NR_126022.1		n.493+24838C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2A42	ENST00000641810.1	MANE Select	c.202G>A	p.Val68Ile	missense	Exon 3 of 3	ENSP00000493333.1	Q8NGT9
	ARHGEF35-AS1	ENST00000460955.5	TSL:4	n.493+24838C>T		intron	N/A
	ARHGEF35-AS1	ENST00000464929.6	TSL:5	n.568-6401C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000737 AC: 8 AN: 108576 Hom.: 1 Cov.: 15

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000163

Gnomad ASJ AF: 0.00101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000382

Gnomad OTH AF: 0.000659

GnomAD2 exomes AF: 0.000113 AC: 20 AN: 177746 AF XY: 0.000137

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000167

Gnomad ASJ exome AF: 0.00165

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000919 AC: 55 AN: 598182 Hom.: 7 Cov.: 6 AF XY: 0.0000929 AC XY: 30 AN XY: 322950

African (AFR) AF: 0.00 AC: 0 AN: 15260

American (AMR) AF: 0.000143 AC: 6 AN: 41938

Ashkenazi Jewish (ASJ) AF: 0.00146 AC: 29 AN: 19810

East Asian (EAS) AF: 0.0000563 AC: 2 AN: 35526

South Asian (SAS) AF: 0.0000467 AC: 3 AN: 64218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3260

European-Non Finnish (NFE) AF: 0.0000264 AC: 9 AN: 341152

Other (OTH) AF: 0.000190 AC: 6 AN: 31544

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000737 AC: 8 AN: 108576 Hom.: 1 Cov.: 15 AF XY: 0.0000193 AC XY: 1 AN XY: 51918

African (AFR) AF: 0.00 AC: 0 AN: 23356

American (AMR) AF: 0.000163 AC: 2 AN: 12272

Ashkenazi Jewish (ASJ) AF: 0.00101 AC: 3 AN: 2966

East Asian (EAS) AF: 0.00 AC: 0 AN: 4690

South Asian (SAS) AF: 0.00 AC: 0 AN: 3334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.0000382 AC: 2 AN: 52400

Other (OTH) AF: 0.000659 AC: 1 AN: 1518

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000795 AC: 8

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.66
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.93	T
PhyloP100		-4.6
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.0070
Sift	Benign	0.41	T
Sift4G	Benign	0.43	T
Vest4		0.074
MutPred		0.40		Loss of glycosylation at S63 (P = 0.2896)
MVP		0.043
ClinPred		0.017	T
GERP RS		0.88
gMVP		0.054
Mutation Taster		=100/0	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: rs776548474; hg19: chr7-143929735; COSMIC: COSV66955691; COSMIC: COSV66955691;