1-205303685-G-A

Variant names:

• chr1-205303685-G-A
• NM_030952.3:c.1652C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030952.3(NUAK2):​c.1652C>T​(p.Ser551Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUAK2 NM_030952.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34235957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUAK2	NM_030952.3	c.1652C>T	p.Ser551Phe	missense_variant	Exon 7 of 7	ENST00000367157.6	NP_112214.3
NUAK2	XM_047431309.1	c.1256C>T	p.Ser419Phe	missense_variant	Exon 6 of 6		XP_047287265.1
NUAK2	XM_005245515.5	c.911C>T	p.Ser304Phe	missense_variant	Exon 3 of 3		XP_005245572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUAK2	ENST00000367157.6	c.1652C>T	p.Ser551Phe	missense_variant	Exon 7 of 7	1	NM_030952.3	ENSP00000356125.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1652C>T (p.S551F) alteration is located in exon 7 (coding exon 7) of the NUAK2 gene. This alteration results from a C to T substitution at nucleotide position 1652, causing the serine (S) at amino acid position 551 to be replaced by a phenylalanine (F). 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	Uncertain	0.42
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.071	D
PrimateAI	Uncertain	0.74	T
REVEL	Uncertain	0.40
Sift4G	Uncertain	0.0040	D
Vest4		0.17
MVP		0.89
MPC		0.85
ClinPred		0.99	D
GERP RS		4.8
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-205272813;