15-44379722-C-G

Variant names:

• chr15-44379722-C-G
• rs147833881
• NM_138423.4:c.835C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138423.4(GOLM2):​c.835C>G​(p.His279Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 145,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H279Y) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000069 (0 hom., cov: 31)
• Consequence: GOLM2 NM_138423.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0534029).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138423.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLM2	NM_138423.4	MANE Select	c.835C>G	p.His279Asp	missense	Exon 7 of 10	NP_612432.2
	GOLM2	NM_177974.3		c.835C>G	p.His279Asp	missense	Exon 7 of 9	NP_816929.1	Q6P4E1-2
	GOLM2	NR_157849.2		n.2538C>G		non_coding_transcript_exon	Exon 8 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLM2	ENST00000299957.11	TSL:1 MANE Select	c.835C>G	p.His279Asp	missense	Exon 7 of 10	ENSP00000299957.6	Q6P4E1-4
	GOLM2	ENST00000345795.6	TSL:1	c.835C>G	p.His279Asp	missense	Exon 7 of 9	ENSP00000335063.4	Q6P4E1-2
	GOLM2	ENST00000915850.1		c.820C>G	p.His274Asp	missense	Exon 7 of 10	ENSP00000585909.1

Frequencies

GnomAD3 genomes AF: 0.00000686 AC: 1 AN: 145728 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000686 AC: 1 AN: 145728 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 70626

African (AFR) AF: 0.00 AC: 0 AN: 39622

American (AMR) AF: 0.00 AC: 0 AN: 14196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 4684

South Asian (SAS) AF: 0.00 AC: 0 AN: 4332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66794

Other (OTH) AF: 0.00 AC: 0 AN: 2034

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	12
DANN	Benign	0.91
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.9	M
PhyloP100		1.7
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.18
Sift	Benign	0.50	T
Sift4G	Benign	0.19	T
Polyphen		0.0080	B
Vest4		0.23
MutPred		0.12		Loss of catalytic residue at H279 (P = 0.121)
MVP		0.57
MPC		0.61
ClinPred		0.038	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.21
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147833881; hg19: chr15-44671920;