16-2037459-G-T

Position:

• chr16-2037459-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001130012.3(NHERF2):​c.793-79G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,239,248 control chromosomes in the GnomAD database, including 25,195 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 0.25 (5786 hom., cov: 32)
  • Exomes 𝑓: 0.18 (19409 hom.)
• Consequence: NHERF2 NM_001130012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHERF2	NM_001130012.3	c.793-79G>T		intron_variant		ENST00000424542.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHERF2	ENST00000424542.7	c.793-79G>T		intron_variant		1	NM_001130012.3	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37964 AN: 151854 Hom.: 5780 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.176 AC: 191557 AN: 1087276 Hom.: 19409 AF XY: 0.172 AC XY: 94872 AN XY: 550352

Gnomad4 AFR exome AF: 0.405

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.000491

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.250 AC: 37993 AN: 151972 Hom.: 5786 Cov.: 32 AF XY: 0.246 AC XY: 18266 AN XY: 74294

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0983

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.230

Alfa AF: 0.110 Hom.: 180

Bravo AF: 0.252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12447809; hg19: chr16-2087460; COSMIC: COSV54594353; COSMIC: COSV54594353;