16-83978527-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_019065.3(NECAB2):āc.310C>Gā(p.His104Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.000051 ( 0 hom. )
Consequence
NECAB2
NM_019065.3 missense
NM_019065.3 missense
Scores
1
4
9
Clinical Significance
Conservation
PhyloP100: 7.52
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27062356).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NECAB2 | NM_019065.3 | c.310C>G | p.His104Asp | missense_variant | 3/13 | ENST00000305202.9 | |
NECAB2 | NM_001329748.1 | c.310C>G | p.His104Asp | missense_variant | 3/12 | ||
NECAB2 | NM_001329749.2 | c.87C>G | p.Phe29Leu | missense_variant | 3/12 | ||
NECAB2 | XM_047434240.1 | c.87C>G | p.Phe29Leu | missense_variant | 3/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NECAB2 | ENST00000305202.9 | c.310C>G | p.His104Asp | missense_variant | 3/13 | 1 | NM_019065.3 | P1 | |
NECAB2 | ENST00000565691.5 | c.87C>G | p.Phe29Leu | missense_variant | 2/11 | 1 | |||
NECAB2 | ENST00000681513.1 | n.715C>G | non_coding_transcript_exon_variant | 3/13 | |||||
NECAB2 | ENST00000566836.1 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000461 AC: 7AN: 151950Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251446Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135892
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GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461688Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32AN XY: 727136
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GnomAD4 genome AF: 0.0000461 AC: 7AN: 151950Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74214
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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 | Oct 19, 2021 | The c.310C>G (p.H104D) alteration is located in exon 3 (coding exon 3) of the NECAB2 gene. This alteration results from a C to G substitution at nucleotide position 310, causing the histidine (H) at amino acid position 104 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MutationTaster
Benign
D;D
PROVEAN
Benign
N
Sift
Benign
T
Sift4G
Benign
T
Vest4
MVP
ClinPred
D
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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