chr16-83990522-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_019065.3(NECAB2):āc.488A>Gā(p.Gln163Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
NECAB2
NM_019065.3 missense
NM_019065.3 missense
Scores
2
6
11
Clinical Significance
Conservation
PhyloP100: 7.37
Genes affected
NECAB2 (HGNC:23746): (N-terminal EF-hand calcium binding protein 2) The protein encoded by this gene is a neuronal calcium-binding protein that binds to and modulates the function of at least two receptors, adenosine A(2A) receptor and metabotropic glutamate receptor type 5. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NECAB2 | NM_019065.3 | c.488A>G | p.Gln163Arg | missense_variant | 6/13 | ENST00000305202.9 | |
NECAB2 | NM_001329748.1 | c.488A>G | p.Gln163Arg | missense_variant | 6/12 | ||
NECAB2 | NM_001329749.2 | c.239A>G | p.Gln80Arg | missense_variant | 5/12 | ||
NECAB2 | XM_047434240.1 | c.239A>G | p.Gln80Arg | missense_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NECAB2 | ENST00000305202.9 | c.488A>G | p.Gln163Arg | missense_variant | 6/13 | 1 | NM_019065.3 | P1 | |
NECAB2 | ENST00000565691.5 | c.239A>G | p.Gln80Arg | missense_variant | 4/11 | 1 | |||
NECAB2 | ENST00000566836.1 | c.161A>G | p.Gln54Arg | missense_variant | 4/7 | 5 | |||
NECAB2 | ENST00000681513.1 | n.893A>G | non_coding_transcript_exon_variant | 6/13 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000360 AC: 9AN: 250326Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135344
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727242
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2023 | The c.488A>G (p.Q163R) alteration is located in exon 6 (coding exon 6) of the NECAB2 gene. This alteration results from a A to G substitution at nucleotide position 488, causing the glutamine (Q) at amino acid position 163 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0134);.;.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at