chr3-183207754-G-A

Variant summary

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

The NM_015078.4(MCF2L2):​c.2566C>T​(p.Arg856Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0002 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

MCF2L2
NM_015078.4 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73
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]

Genome browser will be placed here

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=0.14992753).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MCF2L2NM_015078.4 linkuse as main transcriptc.2566C>T p.Arg856Cys missense_variant 23/30 ENST00000328913.8
MCF2L2XM_017005943.3 linkuse as main transcriptc.2566C>T p.Arg856Cys missense_variant 23/26
MCF2L2XM_011512585.3 linkuse as main transcriptc.1507C>T p.Arg503Cys missense_variant 15/22
MCF2L2XM_047447751.1 linkuse as main transcriptc.1465C>T p.Arg489Cys missense_variant 14/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MCF2L2ENST00000328913.8 linkuse as main transcriptc.2566C>T p.Arg856Cys missense_variant 23/305 NM_015078.4 A2Q86YR7-1
MCF2L2ENST00000473233.5 linkuse as main transcriptc.2566C>T p.Arg856Cys missense_variant 23/295 P4Q86YR7-4
MCF2L2ENST00000488149.5 linkuse as main transcriptn.7013C>T non_coding_transcript_exon_variant 24/282

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152158
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000118
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000756
AC:
19
AN:
251224
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135782
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
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:
0.000123
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000211
AC:
309
AN:
1461872
Hom.:
0
Cov.:
33
AF XY:
0.000210
AC XY:
153
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000254
Gnomad4 OTH exome
AF:
0.000331
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152158
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000203
Hom.:
1
Bravo
AF:
0.000189
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000218
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 submitterclinical testingAmbry GeneticsSep 27, 2022The c.2566C>T (p.R856C) alteration is located in exon 23 (coding exon 23) of the MCF2L2 gene. This alteration results from a C to T substitution at nucleotide position 2566, causing the arginine (R) at amino acid position 856 to be replaced by a cysteine (C). 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
0.18
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.47
CADD
Uncertain
23
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.013
T;.
Eigen
Benign
0.020
Eigen_PC
Benign
-0.068
FATHMM_MKL
Benign
0.36
N
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.9
L;L
MutationTaster
Benign
0.92
D;D
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.13
Sift
Uncertain
0.022
D;D
Sift4G
Uncertain
0.010
D;D
Polyphen
1.0
D;.
Vest4
0.36
MVP
0.30
MPC
0.69
ClinPred
0.52
D
GERP RS
3.9
Varity_R
0.078
gMVP
0.44

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.

Other links and lift over

dbSNP: rs148585637; hg19: chr3-182925542; COSMIC: COSV61060878; COSMIC: COSV61060878; API