Variant 16-83968721-C-G 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.73C>G(p.Arg25Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000693 in 144,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.0000069 ( 0 hom., cov: 30)

Consequence

NECAB2
NM_019065.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.608

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=0.16472605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECAB2	NM_019065.3 link	c.73C>G	p.Arg25Gly	missense_variant	1/13	ENST00000305202.9	NP_061938.2	Q7Z6G3-1
NECAB2	NM_001329748.1 link	c.73C>G	p.Arg25Gly	missense_variant	1/12		NP_001316677.1
NECAB2	NM_001329749.2 link	c.-151C>G		5_prime_UTR_variant	1/12		NP_001316678.1	Q7Z6G3-2
NECAB2	XM_047434240.1 link	c.-22-3430C>G		intron_variant			XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECAB2	ENST00000305202.9 link	c.73C>G	p.Arg25Gly	missense_variant	1/13	1	NM_019065.3	ENSP00000307449.4		Q7Z6G3-1
NECAB2	ENST00000681513.1 link	n.478C>G		non_coding_transcript_exon_variant	1/13

Frequencies

GnomAD3 genomes

AF:

0.00000693

AC:

AN:

144362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000250

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000693

AC:

AN:

144362

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

70202

show subpopulations

Gnomad4 AFR

AF:

0.0000250

Gnomad4 AMR

AF:

0.00

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:

0.00

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 12, 2024

The c.73C>G (p.R25G) alteration is located in exon 1 (coding exon 1) of the NECAB2 gene. This alteration results from a C to G substitution at nucleotide position 73, causing the arginine (R) at amino acid position 25 to be replaced by a glycine (G). 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

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0082

Eigen

Benign

-0.099

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.47

M_CAP

Benign

0.018

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.91

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.048

Polyphen

0.96

Vest4

0.089

MutPred

0.34

Loss of MoRF binding (P = 0.0084);

MVP

0.31

ClinPred

0.35

GERP RS

1.7

Varity_R

0.23

gMVP

0.37

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