chr16-2036468-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001130012.3(NHERF2):c.559C>T(p.Arg187Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 1,601,318 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0025 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0036 ( 16 hom. )
Consequence
NHERF2
NM_001130012.3 missense
NM_001130012.3 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: -0.179
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008509934).
BP6
?
Variant 16-2036468-C-T is Benign according to our data. Variant chr16-2036468-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645965.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 384 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHERF2 | NM_001130012.3 | c.559C>T | p.Arg187Cys | missense_variant | 3/7 | ENST00000424542.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHERF2 | ENST00000424542.7 | c.559C>T | p.Arg187Cys | missense_variant | 3/7 | 1 | NM_001130012.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00252 AC: 384AN: 152222Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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33
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GnomAD3 exomes AF: 0.00254 AC: 569AN: 223876Hom.: 3 AF XY: 0.00273 AC XY: 334AN XY: 122528
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GnomAD4 exome AF: 0.00362 AC: 5246AN: 1448978Hom.: 16 Cov.: 32 AF XY: 0.00357 AC XY: 2567AN XY: 719892
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GnomAD4 genome ? AF: 0.00251 AC: 383AN: 152340Hom.: 0 Cov.: 33 AF XY: 0.00239 AC XY: 178AN XY: 74488
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ESP6500AA
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ExAC
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307
Asia WGS
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3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | NHERF2: BP4, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;.;.
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at