Variant rs1132368 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001130012.3(NHERF2):c.816G>A(p.Ser272=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 1,612,118 control chromosomes in the GnomAD database, including 1,881 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.061 ( 369 hom., cov: 33)

Exomes 𝑓: 0.042 ( 1512 hom. )

Consequence

NHERF2
NM_001130012.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.08

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP7

Synonymous conserved (PhyloP=-5.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHERF2	NM_001130012.3 linkuse as main transcript	c.816G>A	p.Ser272=	synonymous_variant	6/7	ENST00000424542.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHERF2	ENST00000424542.7 linkuse as main transcript	c.816G>A	p.Ser272=	synonymous_variant	6/7	1	NM_001130012.3	P1	Q15599-1

Frequencies

GnomAD3 genomes

AF:

0.0614

AC:

9343

AN:

152136

Hom.:

368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.0707

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.0347

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.0173

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.0443

Gnomad OTH

AF:

0.0674

GnomAD3 exomes

AF:

0.0429

AC:

10548

AN:

245606

Hom.:

299

AF XY:

0.0411

AC XY:

5490

AN XY:

133444

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.0501

Gnomad ASJ exome

AF:

0.0593

Gnomad EAS exome

AF:

0.0357

Gnomad SAS exome

AF:

0.0143

Gnomad FIN exome

AF:

0.0151

Gnomad NFE exome

AF:

0.0446

Gnomad OTH exome

AF:

0.0440

GnomAD4 exome

AF:

0.0423

AC:

61682

AN:

1459864

Hom.:

1512

Cov.:

AF XY:

0.0417

AC XY:

30243

AN XY:

725974

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.0497

Gnomad4 ASJ exome

AF:

0.0615

Gnomad4 EAS exome

AF:

0.0313

Gnomad4 SAS exome

AF:

0.0153

Gnomad4 FIN exome

AF:

0.0185

Gnomad4 NFE exome

AF:

0.0426

Gnomad4 OTH exome

AF:

0.0486

GnomAD4 genome

AF:

0.0614

AC:

9356

AN:

152254

Hom.:

369

Cov.:

AF XY:

0.0598

AC XY:

4454

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0706

Gnomad4 ASJ

AF:

0.0608

Gnomad4 EAS

AF:

0.0350

Gnomad4 SAS

AF:

0.0155

Gnomad4 FIN

AF:

0.0173

Gnomad4 NFE

AF:

0.0443

Gnomad4 OTH

AF:

0.0662

Alfa

AF:

0.0481

Hom.:

526

Bravo

AF:

0.0667

Asia WGS

AF:

0.0290

AC:

101

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.77

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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