15-44379722-C-T

Position:

chr15-44379722-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_138423.4(GOLM2):c.835C>T(p.His279Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000647 in 1,469,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

GOLM2
NM_138423.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.68

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015815377).

BP6

Variant 15-44379722-C-T is Benign according to our data. Variant chr15-44379722-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2471371.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GOLM2	NM_138423.4 linkuse as main transcript	c.835C>T	p.His279Tyr	missense_variant	7/10	ENST00000299957.11	NP_612432.2
GOLM2	NM_177974.3 linkuse as main transcript	c.835C>T	p.His279Tyr	missense_variant	7/9		NP_816929.1
GOLM2	NR_157849.2 linkuse as main transcript	n.2538C>T		non_coding_transcript_exon_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GOLM2	ENST00000299957.11 linkuse as main transcript	c.835C>T	p.His279Tyr	missense_variant	7/10	1	NM_138423.4	ENSP00000299957.6	Q6P4E1-4
GOLM2	ENST00000345795.6 linkuse as main transcript	c.835C>T	p.His279Tyr	missense_variant	7/9	1		ENSP00000335063.4	Q6P4E1-2
GOLM2	ENST00000650436.1 linkuse as main transcript	c.478C>T	p.His160Tyr	missense_variant	9/12			ENSP00000496905.1	A0A3B3IRW9
GOLM2	ENST00000558847.1 linkuse as main transcript	c.175C>T	p.His59Tyr	missense_variant	2/4	3		ENSP00000453465.1	H0YM51

Frequencies

GnomAD3 genomes

AF:

0.000336

AC:

AN:

145728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00124

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000836

AC:

AN:

251178

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0000868

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000348

AC:

AN:

1323518

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

657100

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.0000743

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.000336

AC:

AN:

145842

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

AN XY:

70742

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000278

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 06, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.81

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.24

T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.85

L;.;L

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.4

N;.;N

REVEL

Benign

0.17

Sift

Benign

0.94

T;.;T

Sift4G

Benign

0.85

T;.;T

Polyphen

0.0

.;.;B

Vest4

0.13

MVP

0.59

MPC

0.49

ClinPred

0.0069

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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