Genetic Variant NHERF2:c.*600A>G (chr16-2038584-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001130012.3(NHERF2):c.*600A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 319,392 control chromosomes in the GnomAD database, including 224 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 0.029 ( 120 hom., cov: 32)

Exomes 𝑓: 0.028 ( 104 hom. )

Consequence

NHERF2
NM_001130012.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.22

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0807 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
NHERF2	NM_001130012.3	MANE Select	c.*600A>G	3_prime_UTR	Exon 7 of 7	NP_001123484.1
NHERF2	NM_004785.6		c.*600A>G	3_prime_UTR	Exon 7 of 7	NP_004776.3
NHERF2	NM_001252073.2		c.*600A>G	3_prime_UTR	Exon 6 of 6	NP_001239002.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NHERF2	ENST00000424542.7	TSL:1 MANE Select	c.*600A>G	3_prime_UTR	Exon 7 of 7	ENSP00000408005.2
NHERF2	ENST00000432365.6	TSL:1	c.*600A>G	downstream_gene	N/A	ENSP00000402857.2
NHERF2	ENST00000566198.1	TSL:2	c.*600A>G	downstream_gene	N/A	ENSP00000456895.1

Frequencies

GnomAD3 genomes

AF:

0.0288

AC:

4359

AN:

151340

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00630

Gnomad AMI

AF:

0.0982

Gnomad AMR

AF:

0.0847

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.000394

Gnomad SAS

AF:

0.00708

Gnomad FIN

AF:

0.0498

Gnomad MID

AF:

0.0192

Gnomad NFE

AF:

0.0302

Gnomad OTH

AF:

0.0303

GnomAD4 exome

AF:

0.0281

AC:

4714

AN:

167932

Hom.:

104

Cov.:

AF XY:

0.0250

AC XY:

2419

AN XY:

96740

show subpopulations

African (AFR)

AF:

0.00454

AC:

AN:

1762

American (AMR)

AF:

0.101

AC:

356

AN:

3514

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

4678

East Asian (EAS)

AF:

0.000415

AC:

AN:

2412

South Asian (SAS)

AF:

0.00902

AC:

327

AN:

36242

European-Finnish (FIN)

AF:

0.0516

AC:

507

AN:

9828

Middle Eastern (MID)

AF:

0.0156

AC:

AN:

706

European-Non Finnish (NFE)

AF:

0.0321

AC:

3234

AN:

100612

Other (OTH)

AF:

0.0269

AC:

220

AN:

8178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

216

433

649

866

1082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0288

AC:

4359

AN:

151460

Hom.:

120

Cov.:

AF XY:

0.0298

AC XY:

2204

AN XY:

74010

show subpopulations

African (AFR)

AF:

0.00628

AC:

259

AN:

41234

American (AMR)

AF:

0.0846

AC:

1290

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

3460

East Asian (EAS)

AF:

0.000395

AC:

AN:

5062

South Asian (SAS)

AF:

0.00729

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.0498

AC:

525

AN:

10550

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0302

AC:

2050

AN:

67800

Other (OTH)

AF:

0.0300

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

214

428

641

855

1069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0292

Hom.:

Bravo

AF:

0.0308

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.6

(source)

DANN

Benign

0.42

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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