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. The variant received -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
• 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKD2	NM_033120.4	MANE Select	c.141+10103A>G		intron	N/A	NP_149111.1
	NKD2	NM_001271082.2		c.141+10103A>G		intron	N/A	NP_001258011.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKD2	ENST00000296849.10	TSL:1 MANE Select	c.141+10103A>G		intron	N/A	ENSP00000296849.5
	NKD2	ENST00000274150.4	TSL:1	c.141+10103A>G		intron	N/A	ENSP00000274150.4
	NKD2	ENST00000866687.1		c.141+10103A>G		intron	N/A	ENSP00000536746.1

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

African (AFR) AF: 0.498 AC: 20671 AN: 41468

American (AMR) AF: 0.947 AC: 14493 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 3438 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 0.998 AC: 4816 AN: 4828

European-Finnish (FIN) AF: 0.998 AC: 10604 AN: 10626

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.994 AC: 67646 AN: 68036

Other (OTH) AF: 0.899 AC: 1901 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.36
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4975579; hg19: chr5-1019778;