rs551438799

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_033120.4(NKD2):​c.367C>A​(p.Arg123Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,611,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R123C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NKD2
NM_033120.4 missense

Scores

1
6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.179
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30696577).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NKD2NM_033120.4 linkc.367C>A p.Arg123Ser missense_variant Exon 6 of 10 ENST00000296849.10 NP_149111.1 Q969F2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NKD2ENST00000296849.10 linkc.367C>A p.Arg123Ser missense_variant Exon 6 of 10 1 NM_033120.4 ENSP00000296849.5 Q969F2-1
NKD2ENST00000274150.4 linkc.367C>A p.Arg123Ser missense_variant Exon 6 of 11 1 ENSP00000274150.4 Q969F2-2
NKD2ENST00000519933.5 linkn.136C>A non_coding_transcript_exon_variant Exon 1 of 4 2

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151780
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1459760
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726148
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151780
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74136
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.34
BayesDel_addAF
Benign
-0.043
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.77
D;.
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.051
FATHMM_MKL
Benign
0.66
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.7
M;M
PrimateAI
Benign
0.26
T
PROVEAN
Pathogenic
-5.3
D;D
REVEL
Benign
0.20
Sift
Benign
0.030
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
0.99
D;P
Vest4
0.33
MutPred
0.38
Gain of disorder (P = 0.0803);Gain of disorder (P = 0.0803);
MVP
0.68
MPC
0.056
ClinPred
0.98
D
GERP RS
3.6
Varity_R
0.69
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs551438799; hg19: chr5-1034386; API