16-2035679-C-A

Variant names:

• chr16-2035679-C-A
• rs2516781
• NM_001130012.3:c.415-645C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130012.3(NHERF2):​c.415-645C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000084 in 833,420 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: NHERF2 NM_001130012.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHERF2	NM_001130012.3	c.415-645C>A		intron_variant	Intron 2 of 6	ENST00000424542.7	NP_001123484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHERF2	ENST00000424542.7	c.415-645C>A		intron_variant	Intron 2 of 6	1	NM_001130012.3	ENSP00000408005.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000840 AC: 7 AN: 833420 Hom.: 0 Cov.: 31 AF XY: 0.0000104 AC XY: 4 AN XY: 384952

African (AFR) AF: 0.00 AC: 0 AN: 15786

American (AMR) AF: 0.00 AC: 0 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5154

East Asian (EAS) AF: 0.00 AC: 0 AN: 3640

South Asian (SAS) AF: 0.00 AC: 0 AN: 16478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1626

European-Non Finnish (NFE) AF: 0.00000918 AC: 7 AN: 762160

Other (OTH) AF: 0.00 AC: 0 AN: 27306

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.8
DANN	Benign	0.74
PhyloP100		-1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2516781; hg19: chr16-2085680;