16-83968832-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019065.3(NECAB2):ā€‹c.184A>Cā€‹(p.Thr62Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000084 in 952,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 0.0000084 ( 0 hom. )

Consequence

NECAB2
NM_019065.3 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.710
Variant links:
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]

Genome browser will be placed here

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=0.10562584).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NECAB2NM_019065.3 linkuse as main transcriptc.184A>C p.Thr62Pro missense_variant 1/13 ENST00000305202.9
NECAB2NM_001329748.1 linkuse as main transcriptc.184A>C p.Thr62Pro missense_variant 1/12
NECAB2NM_001329749.2 linkuse as main transcriptc.-40A>C 5_prime_UTR_variant 1/12
NECAB2XM_047434240.1 linkuse as main transcriptc.-22-3319A>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NECAB2ENST00000305202.9 linkuse as main transcriptc.184A>C p.Thr62Pro missense_variant 1/131 NM_019065.3 P1Q7Z6G3-1
NECAB2ENST00000681513.1 linkuse as main transcriptn.589A>C non_coding_transcript_exon_variant 1/13

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000840
AC:
8
AN:
952882
Hom.:
0
Cov.:
30
AF XY:
0.00000894
AC XY:
4
AN XY:
447226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000874
Gnomad4 NFE exome
AF:
0.00000833
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

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 submitterclinical testingAmbry GeneticsOct 06, 2021The c.184A>C (p.T62P) alteration is located in exon 1 (coding exon 1) of the NECAB2 gene. This alteration results from a A to C substitution at nucleotide position 184, causing the threonine (T) at amino acid position 62 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
22
DANN
Benign
0.93
DEOGEN2
Benign
0.012
T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.65
T
M_CAP
Uncertain
0.21
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.050
N
MutationTaster
Benign
0.68
N
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.065
Sift
Benign
0.21
T
Sift4G
Benign
0.20
T
Polyphen
0.0
B
Vest4
0.17
MutPred
0.27
Gain of disorder (P = 0.0158);
MVP
0.030
ClinPred
0.26
T
GERP RS
1.7
Varity_R
0.38
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-84002437; API