15-44289294-G-C

Variant names:

• chr15-44289294-G-C
• rs540145112
• NM_138423.4:c.265G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138423.4(GOLM2):​c.265G>C​(p.Gly89Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 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: 32)
• Consequence: GOLM2 NM_138423.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64

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]

ACMG classification

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=0.21317616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLM2	NM_138423.4	c.265G>C	p.Gly89Arg	missense_variant	Exon 1 of 10	ENST00000299957.11	NP_612432.2
GOLM2	NM_177974.3	c.265G>C	p.Gly89Arg	missense_variant	Exon 1 of 9		NP_816929.1
GOLM2	NR_157849.2	n.576G>C		non_coding_transcript_exon_variant	Exon 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLM2	ENST00000299957.11	c.265G>C	p.Gly89Arg	missense_variant	Exon 1 of 10	1	NM_138423.4	ENSP00000299957.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Pathogenic	1.0
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.073
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.055	T;T
Polyphen		0.91	.;P
Vest4		0.11
MutPred		0.19		Gain of MoRF binding (P = 0.0214);Gain of MoRF binding (P = 0.0214);
MVP		0.48
MPC		1.2
ClinPred		0.96	D
GERP RS		5.3
gMVP		0.26

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: rs540145112; hg19: chr15-44581492;