chr2-100964091-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_002518.4(NPAS2):c.632C>T(p.Thr211Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
NPAS2
NM_002518.4 missense
NM_002518.4 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 4.45
Genes affected
NPAS2 (HGNC:7895): (neuronal PAS domain protein 2) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors. A similar mouse protein may play a regulatory role in the acquisition of specific types of memory. It also may function as a part of a molecular clock operative in the mammalian forebrain. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, NPAS2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.10075995).
BS2
?
High AC in GnomAdExome at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPAS2 | NM_002518.4 | c.632C>T | p.Thr211Ile | missense_variant | 8/21 | ENST00000335681.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPAS2 | ENST00000335681.10 | c.632C>T | p.Thr211Ile | missense_variant | 8/21 | 1 | NM_002518.4 | P1 | |
NPAS2 | ENST00000448812.5 | c.567-4190C>T | intron_variant | 5 | |||||
NPAS2 | ENST00000486017.5 | n.679C>T | non_coding_transcript_exon_variant | 7/7 | 3 | ||||
NPAS2 | ENST00000492373.1 | n.409C>T | non_coding_transcript_exon_variant | 5/6 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251454Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135892
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GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461764Hom.: 0 Cov.: 30 AF XY: 0.0000358 AC XY: 26AN XY: 727200
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74338
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
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