dbSNP rs2020866: FMO2:p.Arg249* (chr1-171203982-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_001460.5(FMO2):c.745C>T(p.Arg249*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000969 in 1,613,638 control chromosomes in the GnomAD database, including 12 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0044 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 5 hom. )

Consequence

FMO2
NM_001460.5 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0120

Publications

14 publications found

Variant links:

Genes affected

FMO2 (HGNC:3770): (flavin containing dimethylaniline monoxygenase 2) This gene encodes a flavin-containing monooxygenase family member. It is an NADPH-dependent enzyme that catalyzes the N-oxidation of some primary alkylamines through an N-hydroxylamine intermediate. However, some human populations contain an allele (FMO2*2A) with a premature stop codon, resulting in a protein that is C-terminally-truncated, has no catalytic activity, and is likely degraded rapidly. This gene is found in a cluster with other related family members on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

FMO2 links:

ENSG00000225243 (HGNC:):

ENSG00000225243 links:

ENSG00000231424 (HGNC:40240):

ENSG00000231424 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMO2	NM_001460.5 link	c.745C>T	p.Arg249*	stop_gained	Exon 6 of 9	ENST00000209929.10	NP_001451.2	Q99518Q5JPC7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMO2	ENST00000209929.10 link	c.745C>T	p.Arg249*	stop_gained	Exon 6 of 9	1	NM_001460.5	ENSP00000209929.8		Q99518

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

666

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00125

AC:

314

AN:

250824

AF XY:

0.000989

show subpopulations

Gnomad AFR exome

AF:

0.0163

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000971

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000613

AC:

896

AN:

1461436

Hom.:

Cov.:

AF XY:

0.000541

AC XY:

393

AN XY:

727032

show subpopulations

African (AFR)

AF:

0.0149

AC:

499

AN:

33442

American (AMR)

AF:

0.000873

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39676

South Asian (SAS)

AF:

0.000301

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.000868

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000210

AC:

234

AN:

1111716

Other (OTH)

AF:

0.00149

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

142

190

237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00438

AC:

667

AN:

152202

Hom.:

Cov.:

AF XY:

0.00433

AC XY:

322

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0150

AC:

623

AN:

41534

American (AMR)

AF:

0.00150

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000623

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68012

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00172

Hom.:

Bravo

AF:

0.00494

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00157

AC:

191

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.43

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.067

PhyloP100

0.012

Vest4

0.84

GERP RS

4.2

Mutation Taster

=177/23

disease causing (fs/PTC)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over