rs2531213

Positions:

• chr16-2038584-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130012.3(NHERF2):​c.*600A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 319,392 control chromosomes in the GnomAD database, including 224 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 0.029 (120 hom., cov: 32)
  • Exomes 𝑓: 0.028 (104 hom.)
• Consequence: NHERF2 NM_001130012.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHERF2	NM_001130012.3	c.*600A>G		3_prime_UTR_variant	7/7	ENST00000424542.7	NP_001123484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHERF2	ENST00000424542.7	c.*600A>G		3_prime_UTR_variant	7/7	1	NM_001130012.3	ENSP00000408005	P1

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4359 AN: 151340 Hom.: 120 Cov.: 32

Gnomad AFR AF: 0.00630

Gnomad AMI AF: 0.0982

Gnomad AMR AF: 0.0847

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.000394

Gnomad SAS AF: 0.00708

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0303

GnomAD4 exome AF: 0.0281 AC: 4714 AN: 167932 Hom.: 104 Cov.: 0 AF XY: 0.0250 AC XY: 2419 AN XY: 96740

Gnomad4 AFR exome AF: 0.00454

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.0107

Gnomad4 EAS exome AF: 0.000415

Gnomad4 SAS exome AF: 0.00902

Gnomad4 FIN exome AF: 0.0516

Gnomad4 NFE exome AF: 0.0321

Gnomad4 OTH exome AF: 0.0269

GnomAD4 genome AF: 0.0288 AC: 4359 AN: 151460 Hom.: 120 Cov.: 32 AF XY: 0.0298 AC XY: 2204 AN XY: 74010

Gnomad4 AFR AF: 0.00628

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.000395

Gnomad4 SAS AF: 0.00729

Gnomad4 FIN AF: 0.0498

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.0300

Alfa AF: 0.0293 Hom.: 33

Bravo AF: 0.0308

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.42

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: rs2531213; hg19: chr16-2088585;