rs551438799

Variant names:

• chr5-1034271-C-A
• rs551438799
• NM_033120.4:c.367C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-1034271-C-A
• chr5-1034271-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033120.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKD2	NM_033120.4	MANE Select	c.367C>A	p.Arg123Ser	missense	Exon 6 of 10	NP_149111.1	Q969F2-1
	NKD2	NM_001271082.2		c.367C>A	p.Arg123Ser	missense	Exon 6 of 11	NP_001258011.1	Q969F2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKD2	ENST00000296849.10	TSL:1 MANE Select	c.367C>A	p.Arg123Ser	missense	Exon 6 of 10	ENSP00000296849.5	Q969F2-1
	NKD2	ENST00000274150.4	TSL:1	c.367C>A	p.Arg123Ser	missense	Exon 6 of 11	ENSP00000274150.4	Q969F2-2
	NKD2	ENST00000866687.1		c.367C>A	p.Arg123Ser	missense	Exon 7 of 11	ENSP00000536746.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151780 Hom.: 0 Cov.: 33

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

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.00 AC: 0 AN: 86120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111576

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151780 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74136

African (AFR) AF: 0.00 AC: 0 AN: 41284

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67940

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.18
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.20
Sift	Benign	0.030	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.33
MutPred		0.38		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
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs551438799; hg19: chr5-1034386;