chr16-83981077-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_019065.3(NECAB2):āc.409C>Gā(p.Leu137Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,614,012 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 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.00015 ( 0 hom. )
Consequence
NECAB2
NM_019065.3 missense
NM_019065.3 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 0.219
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23858538).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NECAB2 | NM_019065.3 | c.409C>G | p.Leu137Val | missense_variant | 5/13 | ENST00000305202.9 | |
NECAB2 | NM_001329748.1 | c.409C>G | p.Leu137Val | missense_variant | 5/12 | ||
NECAB2 | NM_001329749.2 | c.160C>G | p.Leu54Val | missense_variant | 4/12 | ||
NECAB2 | XM_047434240.1 | c.160C>G | p.Leu54Val | missense_variant | 4/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NECAB2 | ENST00000305202.9 | c.409C>G | p.Leu137Val | missense_variant | 5/13 | 1 | NM_019065.3 | P1 | |
NECAB2 | ENST00000565691.5 | c.160C>G | p.Leu54Val | missense_variant | 3/11 | 1 | |||
NECAB2 | ENST00000566836.1 | c.82C>G | p.Leu28Val | missense_variant | 3/7 | 5 | |||
NECAB2 | ENST00000681513.1 | n.814C>G | non_coding_transcript_exon_variant | 5/13 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251486Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135916
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GnomAD4 exome AF: 0.000147 AC: 215AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.000133 AC XY: 97AN XY: 727246
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74310
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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 | Apr 07, 2022 | The c.409C>G (p.L137V) alteration is located in exon 5 (coding exon 5) of the NECAB2 gene. This alteration results from a C to G substitution at nucleotide position 409, causing the leucine (L) at amino acid position 137 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Benign
T;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MVP
ClinPred
D
GERP RS
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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