rs4975579

Variant names:

• chr5-1019663-A-G
• rs4975579
• NM_033120.4:c.141+10103A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-1019663-A-G
• chr5-1019663-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033120.4(NKD2):​c.141+10103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,236 control chromosomes in the GnomAD database, including 59,192 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (59192 hom., cov: 34)
• Consequence: NKD2 NM_033120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.945

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKD2	NM_033120.4	c.141+10103A>G		intron_variant	Intron 3 of 9	ENST00000296849.10	NP_149111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKD2	ENST00000296849.10	c.141+10103A>G		intron_variant	Intron 3 of 9	1	NM_033120.4	ENSP00000296849.5
NKD2	ENST00000274150.4	c.141+10103A>G		intron_variant	Intron 3 of 10	1		ENSP00000274150.4

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129872 AN: 152118 Hom.: 59177 Cov.: 34

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.899

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.853 AC: 129929 AN: 152236 Hom.: 59192 Cov.: 34 AF XY: 0.859 AC XY: 63944 AN XY: 74436

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.991

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.998

Gnomad4 FIN AF: 0.998

Gnomad4 NFE AF: 0.994

Gnomad4 OTH AF: 0.899

Alfa AF: 0.912 Hom.: 7788

Bravo AF: 0.833

Asia WGS AF: 0.968 AC: 3368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs4975579; hg19: chr5-1019778;