15-44338300-T-A

Variant names:

• chr15-44338300-T-A
• rs371987081
• NM_138423.4:c.785T>A

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.785T>A​(p.Val262Asp) 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 1,461,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. V262G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GOLM2 NM_138423.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 1 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=0.06789154).

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.785T>A	p.Val262Asp	missense	Exon 6 of 10	NP_612432.2
	GOLM2	NM_177974.3		c.785T>A	p.Val262Asp	missense	Exon 6 of 9	NP_816929.1	Q6P4E1-2
	GOLM2	NR_157849.2		n.1096T>A		non_coding_transcript_exon	Exon 6 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLM2	ENST00000299957.11	TSL:1 MANE Select	c.785T>A	p.Val262Asp	missense	Exon 6 of 10	ENSP00000299957.6	Q6P4E1-4
	GOLM2	ENST00000345795.6	TSL:1	c.785T>A	p.Val262Asp	missense	Exon 6 of 9	ENSP00000335063.4	Q6P4E1-2
	GOLM2	ENST00000557945.5	TSL:1	n.*160T>A		non_coding_transcript_exon	Exon 5 of 6	ENSP00000453720.1	Q6P4E1-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251226 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461056 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726862

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111388

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	11
DANN	Benign	0.96
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.034	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-1.2
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.024	D
Polyphen		0.14	B
Vest4		0.35
MutPred		0.14		Loss of methylation at K261 (P = 0.0371)
MVP		0.41
MPC		0.94
ClinPred		0.14	T
GERP RS		-6.3
gMVP		0.39

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: rs371987081; hg19: chr15-44630498;