dbSNP rs144496050: GOLM2:p.His238Pro (chr15-44337899-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_138423.4(GOLM2):c.713A>C(p.His238Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000874 in 1,592,458 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 4 hom. )

Consequence

GOLM2
NM_138423.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.155

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00826472).

BP6

Variant 15-44337899-A-C is Benign according to our data. Variant chr15-44337899-A-C is described in ClinVar as Benign. ClinVar VariationId is 788585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00502 (764/152324) while in subpopulation AFR AF = 0.0174 (724/41574). AF 95% confidence interval is 0.0164. There are 5 homozygotes in GnomAd4. There are 352 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GOLM2	NM_138423.4	MANE Select	c.713A>C	p.His238Pro	missense	Exon 5 of 10	NP_612432.2
GOLM2	NM_177974.3		c.713A>C	p.His238Pro	missense	Exon 5 of 9	NP_816929.1	Q6P4E1-2
GOLM2	NR_157849.2		n.1024A>C		non_coding_transcript_exon	Exon 5 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GOLM2	ENST00000299957.11	TSL:1 MANE Select	c.713A>C	p.His238Pro	missense	Exon 5 of 10	ENSP00000299957.6	Q6P4E1-4
GOLM2	ENST00000345795.6	TSL:1	c.713A>C	p.His238Pro	missense	Exon 5 of 9	ENSP00000335063.4	Q6P4E1-2
GOLM2	ENST00000557945.5	TSL:1	n.*88A>C		non_coding_transcript_exon	Exon 4 of 6	ENSP00000453720.1	Q6P4E1-3

Frequencies

GnomAD3 genomes

AF:

0.00502

AC:

764

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

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:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00133

AC:

303

AN:

227742

AF XY:

0.00101

show subpopulations

Gnomad AFR exome

AF:

0.0175

Gnomad AMR exome

AF:

0.00103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000925

Gnomad OTH exome

AF:

0.000179

GnomAD4 exome

AF:

0.000436

AC:

628

AN:

1440134

Hom.:

Cov.:

AF XY:

0.000411

AC XY:

294

AN XY:

716198

show subpopulations

African (AFR)

AF:

0.0159

AC:

510

AN:

32018

American (AMR)

AF:

0.00117

AC:

AN:

36906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25504

East Asian (EAS)

AF:

0.00

AC:

AN:

39246

South Asian (SAS)

AF:

0.0000247

AC:

AN:

81128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53314

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00000904

AC:

AN:

1106728

Other (OTH)

AF:

0.00102

AC:

AN:

59584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

107

134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00502

AC:

764

AN:

152324

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

352

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0174

AC:

724

AN:

41574

American (AMR)

AF:

0.00209

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

116

154

193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.00571

ESP6500AA

AF:

0.0143

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00143

AC:

174

Asia WGS

AF:

0.00232

AC:

AN:

3468

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.85

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.68

MutationAssessor

Benign

2.0

PhyloP100

0.15

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.24

Sift

Benign

0.088

Sift4G

Benign

0.21

Polyphen

0.63

Vest4

0.28

MVP

0.71

MPC

0.99

ClinPred

0.054

GERP RS

3.0

PromoterAI

0.025

Neutral

(source)

gMVP

0.15

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over