5-1009553-A-C

Position:

• chr5-1009553-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033120.4(NKD2):​c.134A>C​(p.Asp45Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000075 in 1,333,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: NKD2 NM_033120.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714

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

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=0.12394178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKD2	NM_033120.4	c.134A>C	p.Asp45Ala	missense_variant	3/10	ENST00000296849.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKD2	ENST00000296849.10	c.134A>C	p.Asp45Ala	missense_variant	3/10	1	NM_033120.4	P2
NKD2	ENST00000274150.4	c.134A>C	p.Asp45Ala	missense_variant	3/11	1		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1333392 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 657688

Gnomad4 AFR exome AF: 0.0000373

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	-0.097
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.41	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.15
Sift	Benign	0.23	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.99	D;P
Vest4		0.14
MutPred		0.13		Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);
MVP		0.60
MPC		0.11
ClinPred		0.32	T
GERP RS		0.39
Varity_R		0.15
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-1009668;