Genetic Variant NM_001130012.3:c.793-79G>T (chr16-2037459-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001130012.3(NHERF2):c.793-79G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,239,248 control chromosomes in the GnomAD database, including 25,195 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 ( 5786 hom., cov: 32)

Exomes 𝑓: 0.18 ( 19409 hom. )

Consequence

NHERF2
NM_001130012.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.83

Publications

10 publications found

Variant links:

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]

NHERF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NHERF2	NM_001130012.3	MANE Select	c.793-79G>T	intron	N/A	NP_001123484.1	Q15599-1
NHERF2	NM_004785.6		c.793-79G>T	intron	N/A	NP_004776.3	Q15599-2
NHERF2	NM_001252073.2		c.460-79G>T	intron	N/A	NP_001239002.1	Q15599-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NHERF2	ENST00000424542.7	TSL:1 MANE Select	c.793-79G>T	intron	N/A	ENSP00000408005.2	Q15599-1
NHERF2	ENST00000432365.6	TSL:1	c.793-79G>T	intron	N/A	ENSP00000402857.2	Q15599-2
NHERF2	ENST00000901526.1		c.793-79G>T	intron	N/A	ENSP00000571585.1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37964

AN:

151854

Hom.:

5780

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0985

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.232

GnomAD4 exome

AF:

0.176

AC:

191557

AN:

1087276

Hom.:

19409

AF XY:

0.172

AC XY:

94872

AN XY:

550352

show subpopulations

African (AFR)

AF:

0.405

AC:

9935

AN:

24530

American (AMR)

AF:

0.132

AC:

4701

AN:

35498

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

5824

AN:

23066

East Asian (EAS)

AF:

0.000491

AC:

AN:

34622

South Asian (SAS)

AF:

0.101

AC:

7432

AN:

73370

European-Finnish (FIN)

AF:

0.245

AC:

11930

AN:

48716

Middle Eastern (MID)

AF:

0.253

AC:

1262

AN:

4994

European-Non Finnish (NFE)

AF:

0.178

AC:

141579

AN:

794766

Other (OTH)

AF:

0.186

AC:

8877

AN:

47714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

7745

15491

23236

30982

38727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4182

8364

12546

16728

20910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.250

AC:

37993

AN:

151972

Hom.:

5786

Cov.:

AF XY:

0.246

AC XY:

18266

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.422

AC:

17489

AN:

41398

American (AMR)

AF:

0.180

AC:

2752

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

877

AN:

3464

East Asian (EAS)

AF:

0.00155

AC:

AN:

5168

South Asian (SAS)

AF:

0.0983

AC:

474

AN:

4820

European-Finnish (FIN)

AF:

0.255

AC:

2694

AN:

10580

Middle Eastern (MID)

AF:

0.260

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.192

AC:

13014

AN:

67942

Other (OTH)

AF:

0.230

AC:

483

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1328

2655

3983

5310

6638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.110

Hom.:

180

Bravo

AF:

0.252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.16

(source)

DANN

Benign

0.72

PhyloP100

-1.8

Mutation Taster

=12/88

disease causing (long InDel)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: -2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over