5-1034760-T-A
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_033120.4(NKD2):c.431T>A(p.Met144Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00183 in 1,610,730 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 Benign (★★).
Frequency
Genomes: 𝑓 0.0053 ( 7 hom., cov: 33)
Exomes 𝑓: 0.0015 ( 25 hom. )
Consequence
NKD2
NM_033120.4 missense
NM_033120.4 missense
Scores
2
5
11
Clinical Significance
Conservation
PhyloP100: 3.73
Genes affected
NKD2 (HGNC:17046): (NKD inhibitor of WNT signaling pathway 2) This gene encodes a member of a family of proteins that function as negative regulators of Wnt receptor signaling through interaction with Dishevelled family members. The encoded protein participates in the delivery of transforming growth factor alpha-containing vesicles to the cell membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0098873675).
BP6
Variant 5-1034760-T-A is Benign according to our data. Variant chr5-1034760-T-A is described in ClinVar as [Benign]. Clinvar id is 781623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NKD2 | NM_033120.4 | c.431T>A | p.Met144Lys | missense_variant | 7/10 | ENST00000296849.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKD2 | ENST00000296849.10 | c.431T>A | p.Met144Lys | missense_variant | 7/10 | 1 | NM_033120.4 | P2 | |
NKD2 | ENST00000274150.4 | c.431T>A | p.Met144Lys | missense_variant | 7/11 | 1 | A2 | ||
NKD2 | ENST00000519933.5 | n.200T>A | non_coding_transcript_exon_variant | 2/4 | 2 | ||||
NKD2 | ENST00000523688.1 | n.5T>A | non_coding_transcript_exon_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00532 AC: 810AN: 152186Hom.: 7 Cov.: 33
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GnomAD3 exomes AF: 0.00289 AC: 720AN: 249198Hom.: 6 AF XY: 0.00246 AC XY: 332AN XY: 135214
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GnomAD4 exome AF: 0.00147 AC: 2143AN: 1458426Hom.: 25 Cov.: 32 AF XY: 0.00140 AC XY: 1014AN XY: 725064
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GnomAD4 genome AF: 0.00532 AC: 811AN: 152304Hom.: 7 Cov.: 33 AF XY: 0.00509 AC XY: 379AN XY: 74482
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | May 18, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | NKD2: BP4, BS1, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;P
Vest4
MVP
MPC
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