rs1185404837

Variant names:

• chr16-2027059-G-A
• NM_001130012.3:c.54G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-2027059-G-A
• chr16-2027059-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001130012.3(NHERF2):​c.54G>A​(p.Glu18Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000792 in 1,262,074 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: 7.9e-7 (0 hom.)
• Consequence: NHERF2 NM_001130012.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.825

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.825 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHERF2	NM_001130012.3	c.54G>A	p.Glu18Glu	synonymous_variant	Exon 1 of 7	ENST00000424542.7	NP_001123484.1
NHERF2	NM_004785.6	c.54G>A	p.Glu18Glu	synonymous_variant	Exon 1 of 7		NP_004776.3
NHERF2	XM_047434923.1	c.54G>A	p.Glu18Glu	synonymous_variant	Exon 1 of 7		XP_047290879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHERF2	ENST00000424542.7	c.54G>A	p.Glu18Glu	synonymous_variant	Exon 1 of 7	1	NM_001130012.3	ENSP00000408005.2
NHERF2	ENST00000432365.6	c.54G>A	p.Glu18Glu	synonymous_variant	Exon 1 of 7	1		ENSP00000402857.2
NHERF2	ENST00000567504.5	c.186+1393G>A		intron_variant	Intron 1 of 2	3		ENSP00000454361.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.92e-7 AC: 1 AN: 1262074 Hom.: 0 Cov.: 31 AF XY: 0.00000161 AC XY: 1 AN XY: 620752

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000379

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-2077060;