15-49235852-G-A

Variant names:

• chr15-49235852-G-A
• rs2090772143
• NM_002044.4:c.268G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002044.4(GALK2):​c.268G>A​(p.Asp90Asn) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALK2 NM_002044.4 missense, splice_region
• Scores: Splicing: ADA: 0.9873
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.03
• Publications: 0 publications found

Genes affected

GALK2 (HGNC:4119): (galactokinase 2) This gene encodes a highly efficient N-acetylgalactosamine (GalNAc) kinase, which has galactokinase activity when galactose is present at high concentrations. The encoded protein is a member of the GHMP kinase family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]

ENSG00000305168 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALK2	NM_002044.4	c.268G>A	p.Asp90Asn	missense_variant, splice_region_variant	Exon 4 of 10	ENST00000560031.6	NP_002035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALK2	ENST00000560031.6	c.268G>A	p.Asp90Asn	missense_variant, splice_region_variant	Exon 4 of 10	1	NM_002044.4	ENSP00000453129.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.268G>A (p.D90N) alteration is located in exon 4 (coding exon 4) of the GALK2 gene. This alteration results from a G to A substitution at nucleotide position 268, causing the aspartic acid (D) at amino acid position 90 to be replaced by an asparagine (N). 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	Benign	0.11
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;T;T;T;.;T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D;D;.;D;.;D;D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Uncertain	2.2	.;.;M;.;.;.;.;.
PhyloP100		8.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.4	N;N;N;N;N;N;D;N
REVEL	Uncertain	0.42
Sift	Benign	0.30	T;T;T;T;T;T;T;T
Sift4G	Benign	0.35	T;T;T;T;T;T;T;T
Polyphen		0.076	.;.;B;.;.;.;.;.
Vest4		0.73
MutPred		0.34		.;.;Gain of glycosylation at S92 (P = 0.1473);.;.;.;.;.;
MVP		0.94
MPC		0.10
ClinPred		0.77	D
GERP RS		5.7
Varity_R		0.56
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.80
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: rs2090772143; hg19: chr15-49528049;