16-2035294-C-T

Variant names:

• chr16-2035294-C-T
• rs9930956
• NM_001130012.3:c.415-1030C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130012.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHERF2	NM_001130012.3	MANE Select	c.415-1030C>T		intron	N/A	NP_001123484.1
	NHERF2	NM_004785.6		c.415-1030C>T		intron	N/A	NP_004776.3
	NHERF2	NM_001252073.2		c.82-1030C>T		intron	N/A	NP_001239002.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHERF2	ENST00000424542.7	TSL:1 MANE Select	c.415-1030C>T		intron	N/A	ENSP00000408005.2
	NHERF2	ENST00000432365.6	TSL:1	c.415-1030C>T		intron	N/A	ENSP00000402857.2
	NHERF2	ENST00000563587.5	TSL:2	c.97-1030C>T		intron	N/A	ENSP00000455909.1

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

African (AFR) AF: 0.176 AC: 1414 AN: 8040

American (AMR) AF: 0.0484 AC: 28 AN: 578

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 94 AN: 2860

East Asian (EAS) AF: 0.00 AC: 0 AN: 2064

South Asian (SAS) AF: 0.00832 AC: 80 AN: 9612

European-Finnish (FIN) AF: 0.120 AC: 20 AN: 166

Middle Eastern (MID) AF: 0.0276 AC: 27 AN: 978

European-Non Finnish (NFE) AF: 0.0592 AC: 25326 AN: 427926

Other (OTH) AF: 0.0503 AC: 772 AN: 15362

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

African (AFR) AF: 0.184 AC: 7603 AN: 41422

American (AMR) AF: 0.0583 AC: 891 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0351 AC: 122 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4822

European-Finnish (FIN) AF: 0.111 AC: 1173 AN: 10574

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0664 AC: 4510 AN: 67954

Other (OTH) AF: 0.0787 AC: 166 AN: 2110

Alfa AF: 0.0723 Hom.: 593

Bravo AF: 0.0963

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.93
DANN	Benign	0.67
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9930956; hg19: chr16-2085295;