8-38993593-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_078473.3(TM2D2):āc.383A>Gā(p.Glu128Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000348 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000092 ( 0 hom., cov: 33)
Exomes š: 0.00037 ( 0 hom. )
Consequence
TM2D2
NM_078473.3 missense
NM_078473.3 missense
Scores
8
6
5
Clinical Significance
Conservation
PhyloP100: 7.15
Genes affected
TM2D2 (HGNC:24127): (TM2 domain containing 2) The protein encoded by this gene contains a structural module related to that of the seven transmembrane domain G protein-coupled receptor superfamily. This protein has sequence and structural similarities to the beta-amyloid binding protein (BBP), but, unlike BBP, it does not regulate a response to beta-amyloid peptide. This protein may have regulatory roles in cell death or proliferation signal cascades. This gene has multiple alternatively spliced transcript variants which encode two different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.808
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TM2D2 | NM_078473.3 | c.383A>G | p.Glu128Gly | missense_variant | 3/4 | ENST00000456397.7 | NP_510882.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TM2D2 | ENST00000456397.7 | c.383A>G | p.Glu128Gly | missense_variant | 3/4 | 1 | NM_078473.3 | ENSP00000416050 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152226Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000135 AC: 34AN: 251462Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135910
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GnomAD4 exome AF: 0.000374 AC: 547AN: 1461662Hom.: 0 Cov.: 30 AF XY: 0.000370 AC XY: 269AN XY: 727138
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GnomAD4 genome AF: 0.0000920 AC: 14AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74384
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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 | Apr 13, 2022 | The c.383A>G (p.E128G) alteration is located in exon 3 (coding exon 3) of the TM2D2 gene. This alteration results from a A to G substitution at nucleotide position 383, causing the glutamic acid (E) at amino acid position 128 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Benign
D;D;D;D
Sift4G
Uncertain
D;D;D;.
Polyphen
D;D;D;.
Vest4
MVP
MPC
0.31
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