Variant X-70042303-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001002254.1(AWAT2):c.731G>A(p.Arg244His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,209,688 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 5 hem. )

Consequence

AWAT2
NM_001002254.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0500

Variant links:

Genes affected

AWAT2 (HGNC:23251): (acyl-CoA wax alcohol acyltransferase 2) This gene encodes an enzyme belonging to the diacylglycerol acyltransferase family. This enzyme produces wax esters by the esterification of long chain (or wax) alcohols with acyl-CoA-derived fatty acids. It functions in lipid metabolism in the skin, mostly in undifferentiated peripheral sebocytes. This enzyme may also have acyl-CoA:retinol acyltransferase activities, where it catalyzes the synthesis of diacylglycerols and retinyl esters. [provided by RefSeq, May 2010]

AWAT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028020829).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AWAT2	NM_001002254.1 linkuse as main transcript	c.731G>A	p.Arg244His	missense_variant	6/8	ENST00000276101.7	NP_001002254.1
AWAT2	XM_011530876.3 linkuse as main transcript	c.731G>A	p.Arg244His	missense_variant	6/8		XP_011529178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AWAT2	ENST00000276101.7 linkuse as main transcript	c.731G>A	p.Arg244His	missense_variant	6/8	5	NM_001002254.1	ENSP00000421172	P1
AWAT2	ENST00000440401.1 linkuse as main transcript	c.*36G>A		3_prime_UTR_variant, NMD_transcript_variant	3/5	5		ENSP00000427523

Frequencies

GnomAD3 genomes

AF:

0.0000623

AC:

AN:

112298

Hom.:

Cov.:

AF XY:

0.0000871

AC XY:

AN XY:

34456

show subpopulations

Gnomad AFR

AF:

0.000162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000938

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

183185

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67659

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1097390

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

362768

show subpopulations

Gnomad4 AFR exome

AF:

0.000303

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000357

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000623

AC:

AN:

112298

Hom.:

Cov.:

AF XY:

0.0000871

AC XY:

AN XY:

34456

show subpopulations

Gnomad4 AFR

AF:

0.000162

Gnomad4 AMR

AF:

0.0000938

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.731G>A (p.R244H) alteration is located in exon 6 (coding exon 6) of the AWAT2 gene. This alteration results from a G to A substitution at nucleotide position 731, causing the arginine (R) at amino acid position 244 to be replaced by a histidine (H). 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

Benign

0.079

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.93

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.034

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.26

M_CAP

Benign

0.061

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.2

REVEL

Benign

0.042

Sift

Benign

0.54

Sift4G

Benign

0.57

Polyphen

0.0030

Vest4

0.066

MutPred

0.46

Loss of MoRF binding (P = 0.0432);

MVP

0.093

MPC

0.42

ClinPred

0.023

GERP RS

-0.24

Varity_R

0.082

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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