rs11881304
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001271938.2(MEGF8):c.8426G>A(p.Arg2809Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0015 in 1,534,696 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0080 ( 19 hom., cov: 32)
Exomes 𝑓: 0.00078 ( 13 hom. )
Consequence
MEGF8
NM_001271938.2 missense
NM_001271938.2 missense
Scores
3
13
Clinical Significance
Conservation
PhyloP100: 6.53
Genes affected
MEGF8 (HGNC:3233): (multiple EGF like domains 8) The protein encoded by this gene is a single-pass type I membrane protein of unknown function that contains several EGF-like domains, Kelch repeats, and PSI domains. Defects in this gene are a cause of Carpenter syndrome 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0028442144).
BP6
?
Variant 19-42376663-G-A is Benign according to our data. Variant chr19-42376663-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 473352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00798 (1216/152370) while in subpopulation AFR AF= 0.0274 (1140/41586). AF 95% confidence interval is 0.0261. There are 19 homozygotes in gnomad4. There are 558 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 19 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF8 | NM_001271938.2 | c.8426G>A | p.Arg2809Lys | missense_variant | 42/42 | ENST00000251268.11 | |
MEGF8 | NM_001410.3 | c.8225G>A | p.Arg2742Lys | missense_variant | 41/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF8 | ENST00000251268.11 | c.8426G>A | p.Arg2809Lys | missense_variant | 42/42 | 5 | NM_001271938.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00796 AC: 1212AN: 152252Hom.: 19 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1212
AN:
152252
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: 0.00166 AC: 226AN: 136352Hom.: 5 AF XY: 0.00131 AC XY: 96AN XY: 73470
GnomAD3 exomes
AF:
AC:
226
AN:
136352
Hom.:
AF XY:
AC XY:
96
AN XY:
73470
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: 0.000783 AC: 1082AN: 1382326Hom.: 13 Cov.: 31 AF XY: 0.000704 AC XY: 479AN XY: 680622
GnomAD4 exome
AF:
AC:
1082
AN:
1382326
Hom.:
Cov.:
31
AF XY:
AC XY:
479
AN XY:
680622
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: 0.00798 AC: 1216AN: 152370Hom.: 19 Cov.: 32 AF XY: 0.00749 AC XY: 558AN XY: 74512
GnomAD4 genome
?
AF:
AC:
1216
AN:
152370
Hom.:
Cov.:
32
AF XY:
AC XY:
558
AN XY:
74512
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
69
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
150
Asia WGS
AF:
AC:
4
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
MEGF8-related Carpenter syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;B;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
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