1-205303802-G-C

Variant names:

• chr1-205303802-G-C
• rs1429208628
• NM_030952.3:c.1535C>G

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.1535C>G​(p.Ala512Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,916 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. A512V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NUAK2 NM_030952.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02
• 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=0.08763194).

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.1535C>G	p.Ala512Gly	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.1535C>G	p.Ala512Gly	missense	Exon 7 of 7	ENSP00000356125.5	Q9H093

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434916 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 711488

African (AFR) AF: 0.00 AC: 0 AN: 32666

American (AMR) AF: 0.00 AC: 0 AN: 41306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.00 AC: 0 AN: 82254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1098274

Other (OTH) AF: 0.00 AC: 0 AN: 59058

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Benign	0.93
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.0
PrimateAI	Benign	0.35	T
REVEL	Benign	0.078
Sift4G	Benign	0.54	T
Vest4		0.042
MVP		0.79
MPC		0.30
ClinPred		0.11	T
GERP RS		3.2
gMVP		0.062
Mutation Taster		=97/3	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: rs1429208628; hg19: chr1-205272930;