chr16-83972160-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_019065.3(NECAB2):​c.211C>A​(p.Arg71Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NECAB2
NM_019065.3 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.854

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NECAB2NM_019065.3 linkuse as main transcriptc.211C>A p.Arg71Ser missense_variant 2/13 ENST00000305202.9
NECAB2NM_001329748.1 linkuse as main transcriptc.211C>A p.Arg71Ser missense_variant 2/12
NECAB2NM_001329749.2 linkuse as main transcriptc.-13C>A 5_prime_UTR_variant 2/12
NECAB2XM_047434240.1 linkuse as main transcriptc.-13C>A 5_prime_UTR_variant 2/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NECAB2ENST00000305202.9 linkuse as main transcriptc.211C>A p.Arg71Ser missense_variant 2/131 NM_019065.3 P1Q7Z6G3-1
NECAB2ENST00000565691.5 linkuse as main transcriptc.-13C>A 5_prime_UTR_variant 1/111 Q7Z6G3-2
NECAB2ENST00000681513.1 linkuse as main transcriptn.616C>A non_coding_transcript_exon_variant 2/13

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461144
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
726856
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152348
Hom.:
0
Cov.:
33
AF XY:
0.0000268
AC XY:
2
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsJan 04, 2024The c.211C>A (p.R71S) alteration is located in exon 2 (coding exon 2) of the NECAB2 gene. This alteration results from a C to A substitution at nucleotide position 211, causing the arginine (R) at amino acid position 71 to be replaced by a serine (S). 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
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Benign
0.59
D
LIST_S2
Uncertain
0.89
D
M_CAP
Pathogenic
0.37
D
MetaRNN
Pathogenic
0.85
D
MetaSVM
Uncertain
-0.17
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.92
D
PROVEAN
Pathogenic
-4.5
D
REVEL
Uncertain
0.63
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.86
MutPred
0.59
Gain of phosphorylation at R71 (P = 0.0537);
MVP
0.44
ClinPred
0.99
D
GERP RS
3.5
Varity_R
0.75
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: chr16-84005765; API