dbSNP rs768142127: NDFIP2:p.Gly42Glu (chr13-79481328-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019080.3(NDFIP2):c.125G>A(p.Gly42Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,545,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

NDFIP2
NM_019080.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.436

Variant links:

Genes affected

NDFIP2 (HGNC:18537): (Nedd4 family interacting protein 2) Enables WW domain binding activity. Involved in negative regulation of gene expression; negative regulation of transport; and positive regulation of protein ubiquitination. Located in several cellular components, including Golgi apparatus; mitochondrion; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NDFIP2 links:

NDFIP2-AS1 (HGNC:40844): (NDFIP2 antisense RNA 1)

NDFIP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060117662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDFIP2	NM_019080.3 link	c.125G>A	p.Gly42Glu	missense_variant	Exon 1 of 8	ENST00000218652.12	NP_061953.2	Q9NV92
NDFIP2	NM_001394685.1 link	c.125G>A	p.Gly42Glu	missense_variant	Exon 1 of 8		NP_001381614.1
NDFIP2	NM_001161407.2 link	c.125G>A	p.Gly42Glu	missense_variant	Exon 1 of 8		NP_001154879.1	B4DGY6
NDFIP2-AS1	NR_046685.1 link	n.-97C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDFIP2	ENST00000218652.12 link	c.125G>A	p.Gly42Glu	missense_variant	Exon 1 of 8	1	NM_019080.3	ENSP00000218652.7		Q9NV92

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000794

AC:

AN:

138574

Hom.:

AF XY:

0.0000930

AC XY:

AN XY:

75276

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000164

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000372

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000898

Gnomad NFE exome

AF:

0.0000395

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000416

AC:

AN:

1393360

Hom.:

Cov.:

AF XY:

0.0000378

AC XY:

AN XY:

687504

show subpopulations

Gnomad4 AFR exome

AF:

0.0000315

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000919

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000176

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000105

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.48

T;.

M_CAP

Benign

0.0078

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.88

.;N

REVEL

Benign

0.028

Sift

Benign

0.056

.;T

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.0

B;B

Vest4

0.18

MutPred

0.19

Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);

MVP

0.17

MPC

1.4

ClinPred

0.022

GERP RS

0.56

Varity_R

0.066

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over