rs1132368

chr16-2037561-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.08

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]

ACMG classification

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	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	c.816G>A	p.Ser272=	synonymous_variant	6/7	1	NM_001130012.3	P1

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9343 AN: 152136 Hom.: 368 Cov.: 33

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

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.: 33 AF XY: 0.0417 AC XY: 30243 AN XY: 725974

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.: 33 AF XY: 0.0598 AC XY: 4454 AN XY: 74448

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

Other links and lift over

dbSNP: rs1132368; hg19: chr16-2087562; COSMIC: COSV54593062; COSMIC: COSV54593062;