Variant 16-2029711-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001130012.3(NHERF2):c.343G>C(p.Ala115Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NHERF2
NM_001130012.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.75

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08394036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHERF2	NM_001130012.3 linkuse as main transcript	c.343G>C	p.Ala115Pro	missense_variant	2/7	ENST00000424542.7	NP_001123484.1	Q15599-1
NHERF2	NM_004785.6 linkuse as main transcript	c.343G>C	p.Ala115Pro	missense_variant	2/7		NP_004776.3	Q15599-2
NHERF2	XM_047434923.1 linkuse as main transcript	c.343G>C	p.Ala115Pro	missense_variant	2/7		XP_047290879.1
NHERF2	XM_047434924.1 linkuse as main transcript	c.25G>C	p.Ala9Pro	missense_variant	2/7		XP_047290880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHERF2	ENST00000424542.7 linkuse as main transcript	c.343G>C	p.Ala115Pro	missense_variant	2/7	1	NM_001130012.3	ENSP00000408005.2		Q15599-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

191

AN:

146062

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000914

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00115

Gnomad ASJ

AF:

0.000887

Gnomad EAS

AF:

0.00377

Gnomad SAS

AF:

0.00475

Gnomad FIN

AF:

0.00268

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00147

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0186

AC:

11199

AN:

602524

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

5203

AN XY:

313026

show subpopulations

Gnomad4 AFR exome

AF:

0.0168

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.0133

Gnomad4 SAS exome

AF:

0.00320

Gnomad4 FIN exome

AF:

0.00297

Gnomad4 NFE exome

AF:

0.0242

Gnomad4 OTH exome

AF:

0.0161

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00129

AC:

189

AN:

146182

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

104

AN XY:

71084

show subpopulations

Gnomad4 AFR

AF:

0.000887

Gnomad4 AMR

AF:

0.00115

Gnomad4 ASJ

AF:

0.000887

Gnomad4 EAS

AF:

0.00378

Gnomad4 SAS

AF:

0.00450

Gnomad4 FIN

AF:

0.00268

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00146

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.343G>C (p.A115P) alteration is located in exon 2 (coding exon 2) of the SLC9A3R2 gene. This alteration results from a G to C substitution at nucleotide position 343, causing the alanine (A) at amino acid position 115 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.37

CADD

Benign

0.75

DANN

Benign

0.56

DEOGEN2

Benign

0.039

.;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.63

T;T;T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.084

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;L;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.19

N;N;N;N

REVEL

Benign

0.011

Sift

Benign

0.14

T;T;T;D

Sift4G

Uncertain

0.047

D;T;T;T

Polyphen

0.0

.;B;.;.

Vest4

0.15, 0.20, 0.18

MutPred

0.37

.;Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);.;

MVP

0.61

MPC

0.059

ClinPred

0.038

GERP RS

-1.4

Varity_R

0.031

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over