19-48470448-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004228.7(CYTH2):āc.115G>Cā(p.Glu39Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
CYTH2
NM_004228.7 missense
NM_004228.7 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 7.06
Genes affected
CYTH2 (HGNC:9502): (cytohesin 2) The protein encoded by this gene is a member of the PSCD family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. The encoded protein exhibits GEP activity in vitro with ARF1, ARF3, and ARF6 and is 83% homologous to CYTH1. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461784Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727198
GnomAD4 exome
AF:
AC:
1
AN:
1461784
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727198
Gnomad4 AFR exome
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Gnomad4 OTH exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
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 | Oct 20, 2021 | The c.115G>C (p.E39Q) alteration is located in exon 2 (coding exon 2) of the CYTH2 gene. This alteration results from a G to C substitution at nucleotide position 115, causing the glutamic acid (E) at amino acid position 39 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
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;.;M;.
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;.;.;.;N
REVEL
Benign
Sift
Benign
.;T;.;.;.;D
Sift4G
Uncertain
D;T;T;.;.;T
Polyphen
0.93
.;P;.;.;.;.
Vest4
0.21, 0.20
MutPred
0.33
.;Gain of MoRF binding (P = 0.0372);Gain of MoRF binding (P = 0.0372);Gain of MoRF binding (P = 0.0372);Gain of MoRF binding (P = 0.0372);.;
MVP
MPC
1.4
ClinPred
D
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
Publications
No publications associated with this variant yet.