Variant 3-183206172-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015078.4(MCF2L2):c.2755A>G(p.Arg919Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MCF2L2
NM_015078.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

MCF2L2 (HGNC:30319): (MCF.2 cell line derived transforming sequence-like 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

MCF2L2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MCF2L2	NM_015078.4 linkuse as main transcript	c.2755A>G	p.Arg919Gly	missense_variant	24/30	ENST00000328913.8
MCF2L2	XM_017005943.3 linkuse as main transcript	c.2755A>G	p.Arg919Gly	missense_variant	24/26
MCF2L2	XM_011512585.3 linkuse as main transcript	c.1696A>G	p.Arg566Gly	missense_variant	16/22
MCF2L2	XM_047447751.1 linkuse as main transcript	c.1654A>G	p.Arg552Gly	missense_variant	15/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2L2	ENST00000328913.8 linkuse as main transcript	c.2755A>G	p.Arg919Gly	missense_variant	24/30	5	NM_015078.4	A2	Q86YR7-1
MCF2L2	ENST00000473233.5 linkuse as main transcript	c.2755A>G	p.Arg919Gly	missense_variant	24/29	5		P4	Q86YR7-4
MCF2L2	ENST00000468976.5 linkuse as main transcript	n.136A>G		non_coding_transcript_exon_variant	2/6	4
MCF2L2	ENST00000488149.5 linkuse as main transcript	n.7202A>G		non_coding_transcript_exon_variant	25/28	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251398

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135866

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Aug 28, 2023

The c.2755A>G (p.R919G) alteration is located in exon 24 (coding exon 24) of the MCF2L2 gene. This alteration results from a A to G substitution at nucleotide position 2755, causing the arginine (R) at amino acid position 919 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

0.21

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0060

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-4.2

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.42

B;.

Vest4

0.42

MutPred

0.70

Loss of MoRF binding (P = 0.0141);Loss of MoRF binding (P = 0.0141);

MVP

0.30

MPC

0.35

ClinPred

0.42

GERP RS

3.1

Varity_R

0.29

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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