dbSNP rs142590512: GOLM2:p.Leu288Ile (chr15-44379749-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138423.4(GOLM2):c.862C>A(p.Leu288Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,451,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

GOLM2
NM_138423.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.220

Variant links:

Genes affected

GOLM2 (HGNC:24892): (golgi membrane protein 2) The increased expression level of this gene is associated with HER-2/neu proto-oncogene overexpression. Amplification and resulting overexpression of this proto-oncogene are found in approximately 30% of human breast and 20% of human ovarian cancers. Alternatively spliced variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Dec 2010]

GOLM2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.095630765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
GOLM2	NM_138423.4 link	c.862C>A	p.Leu288Ile	missense_variant	Exon 7 of 10	ENST00000299957.11	NP_612432.2
GOLM2	NM_177974.3 link	c.862C>A	p.Leu288Ile	missense_variant	Exon 7 of 9		NP_816929.1
GOLM2	NR_157849.2 link	n.2565C>A		non_coding_transcript_exon_variant	Exon 8 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GOLM2	ENST00000299957.11 link	c.862C>A	p.Leu288Ile	missense_variant	Exon 7 of 10	1	NM_138423.4	ENSP00000299957.6	Q6P4E1-4
GOLM2	ENST00000345795.6 link	c.862C>A	p.Leu288Ile	missense_variant	Exon 7 of 9	1		ENSP00000335063.4	Q6P4E1-2
GOLM2	ENST00000650436.1 link	c.505C>A	p.Leu169Ile	missense_variant	Exon 9 of 12			ENSP00000496905.1	A0A3B3IRW9
GOLM2	ENST00000558847.1 link	c.202C>A	p.Leu68Ile	missense_variant	Exon 2 of 4	3		ENSP00000453465.1	H0YM51

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251344

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1451222

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

721872

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000543

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.55

T;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.096

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;L

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.37

N;.;N

REVEL

Benign

0.026

Sift

Benign

0.28

T;.;T

Sift4G

Benign

0.32

T;.;T

Polyphen

0.0010

.;.;B

Vest4

0.22

MutPred

0.23

Loss of catalytic residue at L288 (P = 0.1202);.;Loss of catalytic residue at L288 (P = 0.1202);

MVP

0.24

MPC

0.46

ClinPred

0.060

GERP RS

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over