rs12505080

Variant names:

• chr4-37347718-T-C
• rs12505080
• NM_001144990.2:c.241-8648T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144990.2(NWD2):​c.241-8648T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,148 control chromosomes in the GnomAD database, including 5,761 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 0.26 (5761 hom., cov: 33)
• Consequence: NWD2 NM_001144990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.386
• Publications: 6 publications found

Genes affected

NWD2 (HGNC:29229): (NACHT and WD repeat domain containing 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NWD2	NM_001144990.2	c.241-8648T>C		intron_variant	Intron 2 of 6	ENST00000309447.6	NP_001138462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NWD2	ENST00000309447.6	c.241-8648T>C		intron_variant	Intron 2 of 6	5	NM_001144990.2	ENSP00000309501.5

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39389 AN: 152030 Hom.: 5752 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.259 AC: 39417 AN: 152148 Hom.: 5761 Cov.: 33 AF XY: 0.263 AC XY: 19581 AN XY: 74380

African (AFR) AF: 0.154 AC: 6408 AN: 41542

American (AMR) AF: 0.408 AC: 6234 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3472

East Asian (EAS) AF: 0.403 AC: 2085 AN: 5168

South Asian (SAS) AF: 0.284 AC: 1369 AN: 4824

European-Finnish (FIN) AF: 0.268 AC: 2840 AN: 10584

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18673 AN: 67968

Other (OTH) AF: 0.295 AC: 624 AN: 2112

Alfa AF: 0.245 Hom.: 2866

Bravo AF: 0.268

Asia WGS AF: 0.325 AC: 1130 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.9
DANN	Benign	0.88
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs12505080; hg19: chr4-37349340;