Variant chrX-139587755-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001171876.2(MCF2):c.2711A>G(p.Glu904Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000896 in 111,658 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Consequence

MCF2
NM_001171876.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.582

Variant links:

Genes affected

MCF2 (HGNC:6940): (MCF.2 cell line derived transforming sequence) The oncogenic protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that exerts control over some members of the Rho family of small GTPases. Several transcript variants encoding different isoforms have been found for this gene. These isoforms exhibit different expression patterns and varying levels of GEF activity.[provided by RefSeq, Jan 2010]

MCF2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11130944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCF2	NM_001171876.2 link	c.2711A>G	p.Glu904Gly	missense_variant	26/29	ENST00000519895.6	NP_001165347.1	P10911-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCF2	ENST00000519895.6 link	c.2711A>G	p.Glu904Gly	missense_variant	26/29	2	NM_001171876.2	ENSP00000430276.1		P10911-5

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33838

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000957

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33838

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000957

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

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.2711A>G (p.E904G) alteration is located in exon 26 (coding exon 25) of the MCF2 gene. This alteration results from a A to G substitution at nucleotide position 2711, causing the glutamic acid (E) at amino acid position 904 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.9

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

.;T;.;.;T;.;.;.

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.82

T;T;T;T;T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.11

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

.;M;.;.;.;.;M;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.3

.;N;N;N;N;N;N;N

REVEL

Benign

0.013

Sift

Uncertain

0.029

.;D;T;D;D;T;T;T

Sift4G

Benign

0.16

.;T;T;T;T;T;T;T

Polyphen

0.030, 0.10, 0.80

.;B;.;.;.;.;B;P

Vest4

0.079, 0.075, 0.057, 0.077, 0.067

MVP

0.60

MPC

0.29

ClinPred

0.053

GERP RS

2.5

Varity_R

0.12

gMVP

0.12

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