16-2039005-G-A

Position:

• chr16-2039005-G-A

Variant summary

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

The NM_001130012.3(NHERF2):​c.*1021G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,398 control chromosomes in the GnomAD database, including 6,219 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 (6217 hom., cov: 33)
  • Exomes 𝑓: 0.13 (2 hom.)
• Consequence: NHERF2 NM_001130012.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419

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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHERF2	NM_001130012.3	c.*1021G>A		3_prime_UTR_variant	7/7	ENST00000424542.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHERF2	ENST00000424542.7	c.*1021G>A		3_prime_UTR_variant	7/7	1	NM_001130012.3	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37390 AN: 152092 Hom.: 6204 Cov.: 33

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.128 AC: 24 AN: 188 Hom.: 2 Cov.: 0 AF XY: 0.115 AC XY: 14 AN XY: 122

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.246 AC: 37441 AN: 152210 Hom.: 6217 Cov.: 33 AF XY: 0.242 AC XY: 18024 AN XY: 74426

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0904

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.220

Alfa AF: 0.190 Hom.: 3280

Bravo AF: 0.253

Asia WGS AF: 0.0790 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.79

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: rs3211995; hg19: chr16-2089006;