rs563402132

Variant names:

• chr1-205303733-C-G
• rs563402132
• NM_030952.3:c.1604G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-205303733-C-G
• chr1-205303733-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030952.3(NUAK2):​c.1604G>C​(p.Arg535Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,606 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. 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. R535Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: NUAK2 NM_030952.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07595211).

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.1604G>C	p.Arg535Pro	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.1604G>C	p.Arg535Pro	missense	Exon 7 of 7	ENSP00000356125.5	Q9H093

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1386606 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 682252

African (AFR) AF: 0.00 AC: 0 AN: 30948

American (AMR) AF: 0.00 AC: 0 AN: 33288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20882

East Asian (EAS) AF: 0.00 AC: 0 AN: 39150

South Asian (SAS) AF: 0.00 AC: 0 AN: 73682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5362

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076420

Other (OTH) AF: 0.00 AC: 0 AN: 57006

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	2.0
DANN	Benign	0.82
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.0030
PrimateAI	Benign	0.44	T
REVEL	Benign	0.072
Sift4G	Benign	0.10	T
Vest4		0.15
MVP		0.46
MPC		0.39
ClinPred		0.095	T
GERP RS		1.9
gMVP		0.12
Mutation Taster		=81/19	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: rs563402132; hg19: chr1-205272861; COSMIC: COSV65681124;