15-49256654-A-G

Variant names:

• chr15-49256654-A-G
• rs1114003
• NM_002044.4:c.504+17287A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002044.4(GALK2):​c.504+17287A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0603 in 152,172 control chromosomes in the GnomAD database, including 553 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 0.060 (553 hom., cov: 32)
• Consequence: GALK2 NM_002044.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 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.504+17287A>G		intron	N/A	NP_002035.1
	GALK2	NM_001001556.3		c.471+17287A>G		intron	N/A	NP_001001556.1
	GALK2	NM_001289030.2		c.432+17287A>G		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.504+17287A>G		intron	N/A	ENSP00000453129.1
	GALK2	ENST00000327171.7	TSL:1	c.471+17287A>G		intron	N/A	ENSP00000316632.3
	GALK2	ENST00000396509.6	TSL:2	c.432+17287A>G		intron	N/A	ENSP00000379766.2

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9127 AN: 152054 Hom.: 536 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.0537

Gnomad SAS AF: 0.0800

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0603 AC: 9182 AN: 152172 Hom.: 553 Cov.: 32 AF XY: 0.0594 AC XY: 4416 AN XY: 74398

African (AFR) AF: 0.148 AC: 6136 AN: 41502

American (AMR) AF: 0.0278 AC: 424 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3468

East Asian (EAS) AF: 0.0537 AC: 278 AN: 5180

South Asian (SAS) AF: 0.0795 AC: 383 AN: 4818

European-Finnish (FIN) AF: 0.0136 AC: 144 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0244 AC: 1656 AN: 68008

Other (OTH) AF: 0.0492 AC: 104 AN: 2114

Alfa AF: 0.0256 Hom.: 27

Bravo AF: 0.0619

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.63
PhyloP100		-0.054
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: rs1114003; hg19: chr15-49548851;