Genetic Variant NUAK2:p.Arg618Gln (chr1-205303484-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030952.3(NUAK2):c.1853G>A(p.Arg618Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000249 in 1,604,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

NUAK2
NM_030952.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.780

Publications

5 publications found

Variant links:

Genes affected

NUAK2 (HGNC:29558): (NUAK family kinase 2) Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in several processes, including cellular response to glucose starvation; negative regulation of apoptotic process; and protein phosphorylation. Predicted to be active in cytoplasm. Implicated in anencephaly. [provided by Alliance of Genome Resources, Apr 2022]

NUAK2 Gene-Disease associations (from GenCC):

anencephaly 2
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

NUAK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.048259944).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030952.3. 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
	NUAK2	NM_030952.3	MANE Select	c.1853G>A	p.Arg618Gln	missense	Exon 7 of 7	NP_112214.3	Q9H093

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK2	ENST00000367157.6	TSL:1 MANE Select	c.1853G>A	p.Arg618Gln	missense	Exon 7 of 7	ENSP00000356125.5	Q9H093

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000330

AC:

AN:

242456

AF XY:

0.0000306

show subpopulations

Gnomad AFR exome

AF:

0.000371

Gnomad AMR exome

AF:

0.0000597

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:

0.0000165

AC:

AN:

1452272

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

721972

show subpopulations

African (AFR)

AF:

0.000332

AC:

AN:

33172

American (AMR)

AF:

0.0000459

AC:

AN:

43608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25274

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39636

South Asian (SAS)

AF:

0.0000236

AC:

AN:

84668

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52916

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00000542

AC:

AN:

1107328

Other (OTH)

AF:

0.00

AC:

AN:

59964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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

AF:

0.000105

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.000338

AC:

AN:

41464

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000329

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

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

-0.34

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.71

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.71

M_CAP

Benign

0.024

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.93

PhyloP100

0.78

PrimateAI

Benign

0.24

REVEL

Benign

0.039

Sift4G

Benign

0.52

Vest4

0.11

MVP

0.60

MPC

0.31

ClinPred

0.021

GERP RS

2.0

gMVP

0.31

Mutation Taster

=92/8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over