chr17-19780524-T-C

Variant names:

• chr17-19780524-T-C
• NM_014683.4:c.2864A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014683.4(ULK2):​c.2864A>G​(p.Glu955Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ULK2 NM_014683.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.63

Genes affected

ULK2 (HGNC:13480): (unc-51 like autophagy activating kinase 2) This gene encodes a protein that is similar to a serine/threonine kinase in C. elegans which is involved in axonal elongation. The structure of this protein is similar to the C. elegans protein in that both proteins have an N-terminal kinase domain, a central proline/serine rich (PS) domain, and a C-terminal (C) domain. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK2	NM_014683.4	c.2864A>G	p.Glu955Gly	missense_variant	Exon 25 of 27	ENST00000395544.9	NP_055498.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK2	ENST00000395544.9	c.2864A>G	p.Glu955Gly	missense_variant	Exon 25 of 27	1	NM_014683.4	ENSP00000378914.4
ULK2	ENST00000361658.6	c.2864A>G	p.Glu955Gly	missense_variant	Exon 25 of 28	1		ENSP00000354877.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461478 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727022

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.41	T;T
Sift4G	Uncertain	0.050	T;T
Polyphen		1.0	D;D
Vest4		0.78
MutPred		0.30		Gain of MoRF binding (P = 0.0587);Gain of MoRF binding (P = 0.0587);
MVP		0.74
MPC		0.65
ClinPred		0.87	D
GERP RS		5.8
Varity_R		0.27
gMVP		0.39

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: chr17-19683837;