chr16-2037561-G-A

Variant names:

• chr16-2037561-G-A
• rs1132368
• NM_001130012.3:c.816G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.08
• Publications: 9 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130012.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHERF2	NM_001130012.3	MANE Select	c.816G>A	p.Ser272Ser	synonymous	Exon 6 of 7	NP_001123484.1
	NHERF2	NM_004785.6		c.816G>A	p.Ser272Ser	synonymous	Exon 6 of 7	NP_004776.3
	NHERF2	NM_001252073.2		c.483G>A	p.Ser161Ser	synonymous	Exon 5 of 6	NP_001239002.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHERF2	ENST00000424542.7	TSL:1 MANE Select	c.816G>A	p.Ser272Ser	synonymous	Exon 6 of 7	ENSP00000408005.2
	NHERF2	ENST00000432365.6	TSL:1	c.816G>A	p.Ser272Ser	synonymous	Exon 6 of 7	ENSP00000402857.2
	NHERF2	ENST00000563587.5	TSL:2	c.498G>A	p.Ser166Ser	synonymous	Exon 5 of 6	ENSP00000455909.1

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

GnomAD2 exomes AF: 0.0429 AC: 10548 AN: 245606 AF XY: 0.0411

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

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

GnomAD4 genome AF: 0.0614 AC: 9356 AN: 152254 Hom.: 369 Cov.: 33 AF XY: 0.0598 AC XY: 4454 AN XY: 74448

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: 75 AN: 4824

European-Finnish (FIN) AF: 0.0173 AC: 184 AN: 10622

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0443 AC: 3015 AN: 68020

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.77
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)

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

Other links and lift over

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