1-205303789-CGC-GGT

Variant names:

• chr1-205303789-CGC-GGT
• NM_030952.3:c.1546_1548delGCGinsACC
• NUAK2 p.Ala516Thr

Variant summary

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

The NM_030952.3(NUAK2):​c.1546_1548delGCGinsACC​(p.Ala516Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUAK2 NM_030952.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.958
• 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.

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.1546_1548delGCGinsACC	p.Ala516Thr	missense	N/A	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.1546_1548delGCGinsACC	p.Ala516Thr	missense	N/A	ENSP00000356125.5	Q9H093

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.96

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-205272917;