rs11854557

chr15-49280763-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002044.4(GALK2):c.505-1224T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,096 control chromosomes in the GnomAD database, including 5,964 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5964 hom., cov: 32)
• Consequence: GALK2 NM_002044.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALK2	NM_002044.4	c.505-1224T>C		intron_variant		ENST00000560031.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALK2	ENST00000560031.6	c.505-1224T>C		intron_variant		1	NM_002044.4	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38166 AN: 151978 Hom.: 5963 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.251 AC: 38155 AN: 152096 Hom.: 5964 Cov.: 32 AF XY: 0.250 AC XY: 18603 AN XY: 74346

Gnomad4 AFR AF: 0.0842

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.249

Alfa AF: 0.325 Hom.: 11222

Bravo AF: 0.237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.9
Dann	Benign	0.43

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

LitVar

Other links and lift over

dbSNP: rs11854557; hg19: chr15-49572960;