rs2516781

chr16-2035679-C-T

Variant summary

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

The NM_001130012.3(NHERF2):c.415-645C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 985,214 control chromosomes in the GnomAD database, including 43,542 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 0.28 (6618 hom., cov: 33)
  • Exomes 𝑓: 0.30 (36924 hom.)
• Consequence: NHERF2 NM_001130012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHERF2	NM_001130012.3	c.415-645C>T		intron_variant		ENST00000424542.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHERF2	ENST00000424542.7	c.415-645C>T		intron_variant		1	NM_001130012.3	P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42977 AN: 151988 Hom.: 6599 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.297 AC: 247191 AN: 833108 Hom.: 36924 Cov.: 31 AF XY: 0.297 AC XY: 114139 AN XY: 384836

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.368

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.453

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.283 AC: 43040 AN: 152106 Hom.: 6618 Cov.: 33 AF XY: 0.289 AC XY: 21476 AN XY: 74356

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.284

Alfa AF: 0.304 Hom.: 6012

Bravo AF: 0.280

Asia WGS AF: 0.407 AC: 1414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	8.1
Dann	Benign	0.73

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: rs2516781; hg19: chr16-2085680; COSMIC: COSV54594237; COSMIC: COSV54594237;