Variant 16-2036420-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000424542.7(NHERF2):c.511C>T(p.Arg171Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,607,594 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R171P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 27 hom. )

Consequence

NHERF2
ENST00000424542.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.20

Variant links:

Genes affected

NHERF2 (HGNC:11076): (NHERF family PDZ scaffold protein 2) This gene encodes a member of the NHERF family of PDZ scaffolding proteins. These proteins mediate many cellular processes by binding to and regulating the membrane expression and protein-protein interactions of membrane receptors and transport proteins. The encoded protein plays a role in intestinal sodium absorption by regulating the activity of the sodium/hydrogen exchanger 3, and may also regulate the cystic fibrosis transmembrane regulator (CFTR) ion channel. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

NHERF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0154337585).

BP6

Variant 16-2036420-C-T is Benign according to our data. Variant chr16-2036420-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645964.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 519 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHERF2	NM_001130012.3 linkuse as main transcript	c.511C>T	p.Arg171Trp	missense_variant	3/7	ENST00000424542.7	NP_001123484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHERF2	ENST00000424542.7 linkuse as main transcript	c.511C>T	p.Arg171Trp	missense_variant	3/7	1	NM_001130012.3	ENSP00000408005	P1	Q15599-1

Frequencies

GnomAD3 genomes

AF:

0.00341

AC:

519

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00591

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00339

AC:

800

AN:

235794

Hom.:

AF XY:

0.00343

AC XY:

442

AN XY:

128900

show subpopulations

Gnomad AFR exome

AF:

0.000651

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00291

Gnomad FIN exome

AF:

0.00436

Gnomad NFE exome

AF:

0.00510

Gnomad OTH exome

AF:

0.00380

GnomAD4 exome

AF:

0.00543

AC:

7897

AN:

1455250

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

3830

AN XY:

723500

show subpopulations

Gnomad4 AFR exome

AF:

0.000840

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00315

Gnomad4 FIN exome

AF:

0.00336

Gnomad4 NFE exome

AF:

0.00634

Gnomad4 OTH exome

AF:

0.00503

GnomAD4 genome

AF:

0.00341

AC:

519

AN:

152344

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

250

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00282

Gnomad4 NFE

AF:

0.00591

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00425

Hom.:

Bravo

AF:

0.00310

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.000971

AC:

ESP6500EA

AF:

0.00571

AC:

ExAC

AF:

0.00317

AC:

383

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

NHERF2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;.;T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.44

LIST_S2

Pathogenic

0.98

D;D;D;D;D

MetaRNN

Benign

0.015

T;T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Pathogenic

3.0

M;M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.5

D;D;D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Benign

0.10

T;T;T;D;D

Polyphen

1.0

D;.;.;.;.

Vest4

0.69

MVP

0.63

MPC

0.34

ClinPred

0.059

GERP RS

4.0

Varity_R

0.91

gMVP

0.62

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over