Genetic Variant NM_001271783.2:c.206A>G (chr12-29293316-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001271783.2(FAR2):c.206A>G(p.Lys69Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,429,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FAR2
NM_001271783.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Publications

1 publications found

Variant links:

Genes affected

FAR2 (HGNC:25531): (fatty acyl-CoA reductase 2) This gene belongs to the short chain dehydrogenase/reductase superfamily. It encodes a reductase enzyme involved in the first step of wax biosynthesis wherein fatty acids are converted to fatty alcohols. The encoded peroxisomal protein utilizes saturated fatty acids of 16 or 18 carbons as preferred substrates. Alternatively spliced transcript variants have been observed for this gene. Related pseudogenes have been identified on chromosomes 2, 14 and 22. [provided by RefSeq, Nov 2012]

FAR2 links:

ENSG00000257176 (HGNC:58443):

ENSG00000257176 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04588443).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271783.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAR2	NM_001271783.2	MANE Select	c.206A>G	p.Lys69Arg	missense	Exon 3 of 12	NP_001258712.1	Q96K12-1
FAR2	NM_018099.5		c.206A>G	p.Lys69Arg	missense	Exon 3 of 12	NP_060569.3
FAR2	NM_001271784.2		c.-86A>G		5_prime_UTR	Exon 2 of 11	NP_001258713.1	Q96K12-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAR2	ENST00000536681.8	TSL:1 MANE Select	c.206A>G	p.Lys69Arg	missense	Exon 3 of 12	ENSP00000443291.2	Q96K12-1
FAR2	ENST00000182377.8	TSL:1	c.206A>G	p.Lys69Arg	missense	Exon 3 of 12	ENSP00000182377.4	Q96K12-1
FAR2	ENST00000946761.1		c.206A>G	p.Lys69Arg	missense	Exon 3 of 13	ENSP00000616820.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

222594

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

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

AF:

0.00000140

AC:

AN:

1429452

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31476

American (AMR)

AF:

0.00

AC:

AN:

37194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24820

East Asian (EAS)

AF:

0.00

AC:

AN:

38450

South Asian (SAS)

AF:

0.00

AC:

AN:

80714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52918

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1099304

Other (OTH)

AF:

0.00

AC:

AN:

58940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.040

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.69

M_CAP

Benign

0.0022

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.67

PhyloP100

3.3

PrimateAI

Benign

0.46

PROVEAN

Benign

2.3

REVEL

Benign

0.096

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.066

MutPred

0.52

Gain of catalytic residue at F65 (P = 0.0203)

MVP

0.16

MPC

0.37

ClinPred

0.88

GERP RS

3.1

Varity_R

0.054

gMVP

0.23

Mutation Taster

=82/18

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over