6-130869931-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001431.4(EPB41L2):c.2239G>C(p.Glu747Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
EPB41L2
NM_001431.4 missense
NM_001431.4 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 5.27
Genes affected
EPB41L2 (HGNC:3379): (erythrocyte membrane protein band 4.1 like 2) Predicted to enable PH domain binding activity; cytoskeletal protein binding activity; and structural molecule activity. Involved in positive regulation of protein localization to cell cortex. Located in cell junction; nucleoplasm; and plasma membrane. Colocalizes with COP9 signalosome. [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=0.12483293).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPB41L2 | NM_001431.4 | c.2239G>C | p.Glu747Gln | missense_variant | 15/20 | ENST00000337057.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPB41L2 | ENST00000337057.8 | c.2239G>C | p.Glu747Gln | missense_variant | 15/20 | 1 | NM_001431.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152082Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
3
AN:
152082
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000719 AC: 18AN: 250470Hom.: 0 AF XY: 0.0000664 AC XY: 9AN XY: 135448
GnomAD3 exomes
AF:
AC:
18
AN:
250470
Hom.:
AF XY:
AC XY:
9
AN XY:
135448
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1460938Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 726850
GnomAD4 exome
AF:
AC:
22
AN:
1460938
Hom.:
Cov.:
32
AF XY:
AC XY:
11
AN XY:
726850
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74416
GnomAD4 genome
?
AF:
AC:
3
AN:
152200
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74416
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
6
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 | Jan 26, 2022 | The c.2239G>C (p.E747Q) alteration is located in exon 15 (coding exon 14) of the EPB41L2 gene. This alteration results from a G to C substitution at nucleotide position 2239, causing the glutamic acid (E) at amino acid position 747 to be replaced by a glutamine (Q). 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
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D;.;D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N;N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;.;T;D;T;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T;T;.
Polyphen
0.61, 0.32, 0.77
.;P;B;P;B;P;.;B;.;.
Vest4
MVP
MPC
0.54
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at