Variant 15-44337899-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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:

GOLM2 (HGNC:):

GOLM2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GOLM2	NM_138423.4 linkuse as main transcript	c.713A>C	p.His238Pro	missense_variant	5/10	ENST00000299957.11	NP_612432.2
GOLM2	NM_177974.3 linkuse as main transcript	c.713A>C	p.His238Pro	missense_variant	5/9		NP_816929.1
GOLM2	NR_157849.2 linkuse as main transcript	n.1024A>C		non_coding_transcript_exon_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLM2	ENST00000299957.11 linkuse as main transcript	c.713A>C	p.His238Pro	missense_variant	5/10	1	NM_138423.4	ENSP00000299957.6		Q6P4E1-4

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

GnomAD3 exomes

AF:

0.00133

AC:

303

AN:

227742

Hom.:

AF XY:

0.00101

AC XY:

125

AN XY:

123422

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 SAS 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

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.00117

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000247

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000904

Gnomad4 OTH exome

AF:

0.00102

GnomAD4 genome

AF:

0.00502

AC:

764

AN:

152324

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

352

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0174

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00103

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 14, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.85

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

2.0

M;.;M

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

N;.;N

REVEL

Benign

0.24

Sift

Benign

0.088

T;.;T

Sift4G

Benign

0.21

T;.;T

Polyphen

0.63

.;.;P

Vest4

0.28

MVP

0.71

MPC

0.99

ClinPred

0.054

GERP RS

3.0

gMVP

0.15

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over