16-2035294-C-T

Position:

• chr16-2035294-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.415-1030C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 619,598 control chromosomes in the GnomAD database, including 1,959 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 0.096 (1010 hom., cov: 32)
  • Exomes 𝑓: 0.059 (949 hom.)
• Consequence: NHERF2 NM_001130012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHERF2	NM_001130012.3	c.415-1030C>T		intron_variant		ENST00000424542.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHERF2	ENST00000424542.7	c.415-1030C>T		intron_variant		1	NM_001130012.3	P1

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14529 AN: 151894 Hom.: 998 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.0795

GnomAD4 exome AF: 0.0594 AC: 27761 AN: 467586 Hom.: 949 AF XY: 0.0588 AC XY: 12911 AN XY: 219416

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.0484

Gnomad4 ASJ exome AF: 0.0329

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00832

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.0592

Gnomad4 OTH exome AF: 0.0503

GnomAD4 genome AF: 0.0959 AC: 14579 AN: 152012 Hom.: 1010 Cov.: 32 AF XY: 0.0950 AC XY: 7058 AN XY: 74298

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0583

Gnomad4 ASJ AF: 0.0351

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0664

Gnomad4 OTH AF: 0.0787

Alfa AF: 0.0609 Hom.: 223

Bravo AF: 0.0963

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.93
DANN	Benign	0.67

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: rs9930956; hg19: chr16-2085295;