dbSNP rs1132368: NHERF2:p.Ser272Ser (chr16-2037561-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001130012.3(NHERF2):c.816G>A(p.Ser272Ser) 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

Publications

9 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NHERF2	NM_001130012.3 link	c.816G>A	p.Ser272Ser	synonymous_variant	Exon 6 of 7	ENST00000424542.7	NP_001123484.1	Q15599-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHERF2	ENST00000424542.7 link	c.816G>A	p.Ser272Ser	synonymous_variant	Exon 6 of 7	1	NM_001130012.3	ENSP00000408005.2		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

GnomAD2 exomes

AF:

0.0429

AC:

10548

AN:

245606

AF XY:

0.0411

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 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

African (AFR)

AF:

0.112

AC:

3758

AN:

33452

American (AMR)

AF:

0.0497

AC:

2210

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.0615

AC:

1603

AN:

26052

East Asian (EAS)

AF:

0.0313

AC:

1243

AN:

39672

South Asian (SAS)

AF:

0.0153

AC:

1312

AN:

85752

European-Finnish (FIN)

AF:

0.0185

AC:

984

AN:

53314

Middle Eastern (MID)

AF:

0.0541

AC:

312

AN:

5764

European-Non Finnish (NFE)

AF:

0.0426

AC:

47328

AN:

1111048

Other (OTH)

AF:

0.0486

AC:

2932

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

3123

6246

9368

12491

15614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0614

AC:

9356

AN:

152254

Hom.:

369

Cov.:

AF XY:

0.0598

AC XY:

4454

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.104

AC:

4314

AN:

41528

American (AMR)

AF:

0.0706

AC:

1081

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0608

AC:

211

AN:

3472

East Asian (EAS)

AF:

0.0350

AC:

181

AN:

5168

South Asian (SAS)

AF:

0.0155

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0173

AC:

184

AN:

10622

Middle Eastern (MID)

AF:

0.106

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0443

AC:

3015

AN:

68020

Other (OTH)

AF:

0.0662

AC:

140

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

437

874

1310

1747

2184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0494

Hom.:

950

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

(source)

DANN

Benign

0.83

PhyloP100

-5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs1132368

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over