rs781358198

Variant names:

• chr12-29293385-C-A
• rs781358198
• NM_001271783.2:c.275C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-29293385-C-A
• chr12-29293385-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001271783.2(FAR2):​c.275C>A​(p.Ala92Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A92V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAR2 NM_001271783.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.761
• Publications: 1 publications found

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]

ENSG00000257176 (HGNC:58443):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33166242).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAR2	NM_001271783.2	MANE Select	c.275C>A	p.Ala92Asp	missense	Exon 3 of 12	NP_001258712.1	Q96K12-1
	FAR2	NM_018099.5		c.275C>A	p.Ala92Asp	missense	Exon 3 of 12	NP_060569.3
	FAR2	NM_001271784.2		c.-17C>A		5_prime_UTR	Exon 2 of 11	NP_001258713.1	Q96K12-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAR2	ENST00000536681.8	TSL:1 MANE Select	c.275C>A	p.Ala92Asp	missense	Exon 3 of 12	ENSP00000443291.2	Q96K12-1
	FAR2	ENST00000182377.8	TSL:1	c.275C>A	p.Ala92Asp	missense	Exon 3 of 12	ENSP00000182377.4	Q96K12-1
	FAR2	ENST00000946761.1		c.275C>A	p.Ala92Asp	missense	Exon 3 of 13	ENSP00000616820.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.76
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.049
Sift	Benign	0.17	T
Sift4G	Benign	0.12	T
Polyphen		0.0060	B
Vest4		0.28
MutPred		0.78		Gain of disorder (P = 0.0342)
MVP		0.15
MPC		0.98
ClinPred		0.21	T
GERP RS		2.3
Varity_R		0.19
gMVP		0.72
Mutation Taster		=65/35	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: rs781358198; hg19: chr12-29446318;