chr10-62204958-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_145307.4(RTKN2):āc.1085A>Gā(p.Asn362Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000549 in 1,601,894 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 (ā ).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 32)
Exomes š: 0.000046 ( 0 hom. )
Consequence
RTKN2
NM_145307.4 missense
NM_145307.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 3.78
Genes affected
RTKN2 (HGNC:19364): (rhotekin 2) Involved in negative regulation of intrinsic apoptotic signaling pathway; positive regulation of NF-kappaB transcription factor activity; and positive regulation of NIK/NF-kappaB signaling. Located in cytoplasm and nucleus. [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=0.1343905).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000839 AC: 20AN: 238362Hom.: 0 AF XY: 0.000108 AC XY: 14AN XY: 129116
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GnomAD4 exome AF: 0.0000455 AC: 66AN: 1449586Hom.: 0 Cov.: 30 AF XY: 0.0000500 AC XY: 36AN XY: 720628
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GnomAD4 genome AF: 0.000144 AC: 22AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74478
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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 | Nov 15, 2024 | The c.1085A>G (p.N362S) alteration is located in exon 10 (coding exon 10) of the RTKN2 gene. This alteration results from a A to G substitution at nucleotide position 1085, causing the asparagine (N) at amino acid position 362 to be replaced by a serine (S). 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
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;B
Vest4
MVP
MPC
0.079
ClinPred
T
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