Variant 3-183205951-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015078.4(MCF2L2):c.2809G>C(p.Ala937Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MCF2L2
NM_015078.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.262

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04773259).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MCF2L2	NM_015078.4 linkuse as main transcript	c.2809G>C	p.Ala937Pro	missense_variant	25/30	ENST00000328913.8	NP_055893.4
MCF2L2	XM_017005943.3 linkuse as main transcript	c.2809G>C	p.Ala937Pro	missense_variant	25/26		XP_016861432.2
MCF2L2	XM_011512585.3 linkuse as main transcript	c.1750G>C	p.Ala584Pro	missense_variant	17/22		XP_011510887.1
MCF2L2	XM_047447751.1 linkuse as main transcript	c.1708G>C	p.Ala570Pro	missense_variant	16/21		XP_047303707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCF2L2	ENST00000328913.8 linkuse as main transcript	c.2809G>C	p.Ala937Pro	missense_variant	25/30	5	NM_015078.4	ENSP00000328118	A2	Q86YR7-1
MCF2L2	ENST00000473233.5 linkuse as main transcript	c.2809G>C	p.Ala937Pro	missense_variant	25/29	5		ENSP00000420070	P4	Q86YR7-4
MCF2L2	ENST00000468976.5 linkuse as main transcript	n.190G>C		non_coding_transcript_exon_variant	3/6	4
MCF2L2	ENST00000488149.5 linkuse as main transcript	n.7256G>C		non_coding_transcript_exon_variant	26/28	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251060

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

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:

0.00000137

AC:

AN:

1461118

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000824

AC:

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

May 26, 2024

The c.2809G>C (p.A937P) alteration is located in exon 25 (coding exon 25) of the MCF2L2 gene. This alteration results from a G to C substitution at nucleotide position 2809, causing the alanine (A) at amino acid position 937 to be replaced by a proline (P). 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

0.074

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.29

DEOGEN2

Benign

0.0019

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.00092

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.62

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

2.9

N;N

REVEL

Benign

0.097

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.011

B;.

Vest4

0.19

MutPred

0.67

Loss of MoRF binding (P = 0.0769);Loss of MoRF binding (P = 0.0769);

MVP

0.048

MPC

0.24

ClinPred

0.064

GERP RS

-2.9

Varity_R

0.084

gMVP

0.30

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