rs11854557

Variant names:

• chr15-49280763-T-C
• rs11854557
• NM_002044.4:c.505-1224T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002044.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALK2	NM_002044.4	MANE Select	c.505-1224T>C		intron	N/A	NP_002035.1
	GALK2	NM_001001556.3		c.472-1224T>C		intron	N/A	NP_001001556.1
	GALK2	NM_001289030.2		c.433-1224T>C		intron	N/A	NP_001275959.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALK2	ENST00000560031.6	TSL:1 MANE Select	c.505-1224T>C		intron	N/A	ENSP00000453129.1
	GALK2	ENST00000327171.7	TSL:1	c.472-1224T>C		intron	N/A	ENSP00000316632.3
	GALK2	ENST00000396509.6	TSL:2	c.433-1224T>C		intron	N/A	ENSP00000379766.2

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

African (AFR) AF: 0.0842 AC: 3496 AN: 41518

American (AMR) AF: 0.237 AC: 3614 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1434 AN: 3468

East Asian (EAS) AF: 0.111 AC: 572 AN: 5176

South Asian (SAS) AF: 0.173 AC: 834 AN: 4812

European-Finnish (FIN) AF: 0.338 AC: 3568 AN: 10564

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23676 AN: 67970

Other (OTH) AF: 0.249 AC: 524 AN: 2106

Alfa AF: 0.316 Hom.: 13443

Bravo AF: 0.237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.43
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs11854557; hg19: chr15-49572960;