16-2029661-G-A

Position:

chr16-2029661-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000424542.7(NHERF2):c.293G>A(p.Arg98Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000408 in 1,567,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

NHERF2
ENST00000424542.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15408748).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NHERF2	NM_001130012.3 linkuse as main transcript	c.293G>A	p.Arg98Gln	missense_variant	2/7	ENST00000424542.7	NP_001123484.1
NHERF2	NM_004785.6 linkuse as main transcript	c.293G>A	p.Arg98Gln	missense_variant	2/7		NP_004776.3
NHERF2	XM_047434923.1 linkuse as main transcript	c.293G>A	p.Arg98Gln	missense_variant	2/7		XP_047290879.1
NHERF2	XM_047434924.1 linkuse as main transcript	c.-26G>A		5_prime_UTR_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.293G>A	p.Arg98Gln	missense_variant	2/7	1	NM_001130012.3	ENSP00000408005	P1	Q15599-1
NHERF2	ENST00000432365.6 linkuse as main transcript	c.293G>A	p.Arg98Gln	missense_variant	2/7	1		ENSP00000402857		Q15599-2
NHERF2	ENST00000567504.5 linkuse as main transcript	c.266G>A	p.Arg89Gln	missense_variant	2/3	3		ENSP00000454361
NHERF2	ENST00000563587.5 linkuse as main transcript	c.-26G>A		5_prime_UTR_variant	1/6	2		ENSP00000455909

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000287

AC:

AN:

174468

Hom.:

AF XY:

0.0000107

AC XY:

AN XY:

93366

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000758

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000790

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000396

AC:

AN:

1414948

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

699428

show subpopulations

Gnomad4 AFR exome

AF:

0.0000617

Gnomad4 AMR exome

AF:

0.0000532

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000270

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000441

Gnomad4 OTH exome

AF:

0.0000512

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000323

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000259

AC:

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

Apr 29, 2024

The c.293G>A (p.R98Q) alteration is located in exon 2 (coding exon 2) of the SLC9A3R2 gene. This alteration results from a G to A substitution at nucleotide position 293, causing the arginine (R) at amino acid position 98 to be replaced by a glutamine (Q). 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

0.085

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

.;T;.

Eigen

Benign

-0.035

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.045

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;L

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.66

N;N;N

REVEL

Benign

0.036

Sift

Uncertain

0.015

D;T;T

Sift4G

Benign

0.10

T;T;T

Polyphen

0.93

.;P;.

Vest4

0.15, 0.26

MVP

0.88

MPC

0.069

ClinPred

0.11

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.070

gMVP

0.22

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