chr3-183207754-G-A
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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
NM_015078.4 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 3.73
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]
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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=0.14992753).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCF2L2 | NM_015078.4 | c.2566C>T | p.Arg856Cys | missense_variant | 23/30 | ENST00000328913.8 | |
MCF2L2 | XM_017005943.3 | c.2566C>T | p.Arg856Cys | missense_variant | 23/26 | ||
MCF2L2 | XM_011512585.3 | c.1507C>T | p.Arg503Cys | missense_variant | 15/22 | ||
MCF2L2 | XM_047447751.1 | c.1465C>T | p.Arg489Cys | missense_variant | 14/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCF2L2 | ENST00000328913.8 | c.2566C>T | p.Arg856Cys | missense_variant | 23/30 | 5 | NM_015078.4 | A2 | |
MCF2L2 | ENST00000473233.5 | c.2566C>T | p.Arg856Cys | missense_variant | 23/29 | 5 | P4 | ||
MCF2L2 | ENST00000488149.5 | n.7013C>T | non_coding_transcript_exon_variant | 24/28 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152158Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251224Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135782
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GnomAD4 exome AF: 0.000211 AC: 309AN: 1461872Hom.: 0 Cov.: 33 AF XY: 0.000210 AC XY: 153AN XY: 727240
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GnomAD4 genome AF: 0.0000920 AC: 14AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74320
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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 27, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at