Genetic Variant FAXDC2:p.Asp277Asn (chr5-154821276-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_032385.5(FAXDC2):c.829G>A(p.Asp277Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000378 in 1,611,562 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 2 hom. )

Consequence

FAXDC2
NM_032385.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84

Variant links:

Genes affected

FAXDC2 (HGNC:1334): (fatty acid hydroxylase domain containing 2) Predicted to enable C-4 methylsterol oxidase activity. Involved in positive regulation of megakaryocyte differentiation and positive regulation of protein phosphorylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAXDC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAXDC2	NM_032385.5 link	c.829G>A	p.Asp277Asn	missense_variant	Exon 8 of 9	ENST00000326080.10	NP_115761.2	Q96IV6-1
FAXDC2	XM_006714753.3 link	c.829G>A	p.Asp277Asn	missense_variant	Exon 9 of 10		XP_006714816.1	Q96IV6-1
FAXDC2	XM_047416652.1 link	c.409G>A	p.Asp137Asn	missense_variant	Exon 5 of 6		XP_047272608.1
FAXDC2	XM_047416654.1 link	c.409G>A	p.Asp137Asn	missense_variant	Exon 4 of 5		XP_047272610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAXDC2	ENST00000326080.10 link	c.829G>A	p.Asp277Asn	missense_variant	Exon 8 of 9	1	NM_032385.5	ENSP00000320604.5		Q96IV6-1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000296

AC:

AN:

247034

Hom.:

AF XY:

0.000306

AC XY:

AN XY:

134166

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.0000568

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.000604

Gnomad NFE exome

AF:

0.000321

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000392

AC:

572

AN:

1459566

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

284

AN XY:

726082

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.0000899

Gnomad4 ASJ exome

AF:

0.00157

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.000506

Gnomad4 NFE exome

AF:

0.000403

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000243

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000397

Hom.:

Bravo

AF:

0.000185

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.829G>A (p.D277N) alteration is located in exon 8 (coding exon 7) of the FAXDC2 gene. This alteration results from a G to A substitution at nucleotide position 829, causing the aspartic acid (D) at amino acid position 277 to be replaced by an asparagine (N). 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

Pathogenic

0.57

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.51

D;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.023

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.75

MVP

0.32

MPC

0.65

ClinPred

0.84

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.52

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over