dbSNP rs2531213: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHERF2	NM_001130012.3 link	c.*600A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000424542.7	NP_001123484.1	Q15599-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NHERF2	ENST00000424542.7 link	c.*600A>G	3_prime_UTR_variant	Exon 7 of 7	1	NM_001130012.3	ENSP00000408005.2	Q15599-1
NHERF2	ENST00000432365.6 link	c.*600A>G	downstream_gene_variant		1		ENSP00000402857.2	Q15599-2
NHERF2	ENST00000566198.1 link	c.*600A>G	downstream_gene_variant		2		ENSP00000456895.1	Q15599-3

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 v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over