Variant 16-83990504-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_019065.3(NECAB2):c.470G>A(p.Gly157Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,960 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NECAB2
NM_019065.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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]

NECAB2 links:

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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=0.13817438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECAB2	NM_019065.3 link	c.470G>A	p.Gly157Asp	missense_variant	6/13	ENST00000305202.9	NP_061938.2	Q7Z6G3-1
NECAB2	NM_001329748.1 link	c.470G>A	p.Gly157Asp	missense_variant	6/12		NP_001316677.1
NECAB2	NM_001329749.2 link	c.221G>A	p.Gly74Asp	missense_variant	5/12		NP_001316678.1	Q7Z6G3-2
NECAB2	XM_047434240.1 link	c.221G>A	p.Gly74Asp	missense_variant	5/12		XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NECAB2	ENST00000305202.9 link	c.470G>A	p.Gly157Asp	missense_variant	6/13	1	NM_019065.3	ENSP00000307449.4	Q7Z6G3-1
NECAB2	ENST00000565691.5 link	c.221G>A	p.Gly74Asp	missense_variant	4/11	1		ENSP00000457354.1	Q7Z6G3-2
NECAB2	ENST00000566836.1 link	c.143G>A	p.Gly48Asp	missense_variant	4/7	5		ENSP00000455322.1	H3BPH6
NECAB2	ENST00000681513.1 link	n.875G>A		non_coding_transcript_exon_variant	6/13

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

249968

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.00000378

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

Aug 14, 2024

The c.470G>A (p.G157D) alteration is located in exon 6 (coding exon 6) of the NECAB2 gene. This alteration results from a G to A substitution at nucleotide position 470, causing the glycine (G) at amino acid position 157 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

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.016

T;.;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.70

N;N;N

REVEL

Benign

0.073

Sift

Benign

0.54

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.13

B;.;.

Vest4

0.35

MutPred

0.26

Loss of helix (P = 0.0558);.;.;

MVP

0.048

ClinPred

0.11

GERP RS

4.2

Varity_R

0.046

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over