Genetic Variant GALK2:p.Gly434Arg (chr15-49328082-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002044.4(GALK2):c.1300G>A(p.Gly434Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GALK2
NM_002044.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.591

Publications

0 publications found

Variant links:

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]

GALK2 links:

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

FAM227B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057074726).

BP6

Variant 15-49328082-G-A is Benign according to our data. Variant chr15-49328082-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 4027936.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALK2	NM_002044.4 link	c.1300G>A	p.Gly434Arg	missense_variant	Exon 10 of 10	ENST00000560031.6	NP_002035.1	Q01415-1
FAM227B	NM_152647.3 link	c.*486C>T		3_prime_UTR_variant	Exon 16 of 16	ENST00000299338.11	NP_689860.2	Q96M60-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALK2	ENST00000560031.6 link	c.1300G>A	p.Gly434Arg	missense_variant	Exon 10 of 10	1	NM_002044.4	ENSP00000453129.1		Q01415-1
FAM227B	ENST00000299338.11 link	c.*486C>T		3_prime_UTR_variant	Exon 16 of 16	2	NM_152647.3	ENSP00000299338.6		Q96M60-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111968

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 15, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Benign

0.56

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.055

.;T;T;T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.76

T;T;.;.;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.057

T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.080

.;N;.;.;.;.

PhyloP100

0.59

PrimateAI

Benign

0.25

PROVEAN

Benign

0.95

N;N;N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.61

T;T;T;T;T;T

Sift4G

Benign

0.58

T;T;T;T;T;T

Polyphen

0.0

.;B;.;.;.;.

Vest4

0.066

MutPred

0.29

.;Gain of solvent accessibility (P = 0.0097);.;.;.;.;

MVP

0.42

MPC

0.044

ClinPred

0.030

GERP RS

-4.8

Varity_R

0.031

gMVP

0.53

Mutation Taster

=87/13

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over