16-83978527-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019065.3(NECAB2):ā€‹c.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

Scores

1
4
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.52
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 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
NECAB2NM_019065.3 linkuse as main transcriptc.310C>G p.His104Asp missense_variant 3/13 ENST00000305202.9
NECAB2NM_001329748.1 linkuse as main transcriptc.310C>G p.His104Asp missense_variant 3/12
NECAB2NM_001329749.2 linkuse as main transcriptc.87C>G p.Phe29Leu missense_variant 3/12
NECAB2XM_047434240.1 linkuse as main transcriptc.87C>G p.Phe29Leu missense_variant 3/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NECAB2ENST00000305202.9 linkuse as main transcriptc.310C>G p.His104Asp missense_variant 3/131 NM_019065.3 P1Q7Z6G3-1
NECAB2ENST00000565691.5 linkuse as main transcriptc.87C>G p.Phe29Leu missense_variant 2/111 Q7Z6G3-2
NECAB2ENST00000681513.1 linkuse as main transcriptn.715C>G non_coding_transcript_exon_variant 3/13
NECAB2ENST00000566836.1 linkuse as main transcript upstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151950
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000725
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251446
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000703
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000513
AC:
75
AN:
1461688
Hom.:
0
Cov.:
30
AF XY:
0.0000440
AC XY:
32
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 NFE exome
AF:
0.0000666
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000461
AC:
7
AN:
151950
Hom.:
0
Cov.:
32
AF XY:
0.0000539
AC XY:
4
AN XY:
74214
show subpopulations
Gnomad4 AFR
AF:
0.0000725
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000604
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 19, 2021The 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Pathogenic
0.20
CADD
Pathogenic
28
DANN
Benign
0.56
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.27
T
MutationTaster
Benign
1.0
D;D
PROVEAN
Benign
-0.040
N
Sift
Benign
0.075
T
Sift4G
Benign
0.54
T
Vest4
0.22
MVP
0.12
ClinPred
0.57
D
GERP RS
4.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376943166; hg19: chr16-84012132; API