4-37433971-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001144990.2(NWD2):c.657C>T(p.His219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,550,300 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (4 hom.)
• Consequence: NWD2 NM_001144990.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0280

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 4-37433971-C-T is Benign according to our data. Variant chr4-37433971-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.028 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NWD2	NM_001144990.2	c.657C>T	p.His219=	synonymous_variant	5/7	ENST00000309447.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NWD2	ENST00000309447.6	c.657C>T	p.His219=	synonymous_variant	5/7	5	NM_001144990.2	P1

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 206 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.00256

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.00117 AC: 183 AN: 156836 Hom.: 0 AF XY: 0.00123 AC XY: 102 AN XY: 82946

Gnomad AFR exome AF: 0.000746

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000275

Gnomad SAS exome AF: 0.0000440

Gnomad FIN exome AF: 0.000119

Gnomad NFE exome AF: 0.00271

Gnomad OTH exome AF: 0.000682

GnomAD4 exome AF: 0.00231 AC: 3235 AN: 1398096 Hom.: 4 Cov.: 30 AF XY: 0.00224 AC XY: 1548 AN XY: 689574

Gnomad4 AFR exome AF: 0.000443

Gnomad4 AMR exome AF: 0.000420

Gnomad4 ASJ exome AF: 0.0000398

Gnomad4 EAS exome AF: 0.000112

Gnomad4 SAS exome AF: 0.0000506

Gnomad4 FIN exome AF: 0.000142

Gnomad4 NFE exome AF: 0.00283

Gnomad4 OTH exome AF: 0.00243

GnomAD4 genome AF: 0.00135 AC: 206 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.00112 AC XY: 83 AN XY: 74412

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00256

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.00152

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

NWD2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	2.7
Dann	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs183200253; hg19: chr4-37435593;