16-83968803-A-C

Position:

• chr16-83968803-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019065.3(NECAB2):​c.155A>C​(p.Asp52Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: NECAB2 NM_019065.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.96

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04403773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NECAB2	NM_019065.3	c.155A>C	p.Asp52Ala	missense_variant	1/13	ENST00000305202.9
NECAB2	NM_001329748.1	c.155A>C	p.Asp52Ala	missense_variant	1/12
NECAB2	NM_001329749.2	c.-69A>C		5_prime_UTR_variant	1/12
NECAB2	XM_047434240.1	c.-22-3348A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECAB2	ENST00000305202.9	c.155A>C	p.Asp52Ala	missense_variant	1/13	1	NM_019065.3	P1
NECAB2	ENST00000681513.1	n.560A>C		non_coding_transcript_exon_variant	1/13

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.155A>C (p.D52A) 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 155, causing the aspartic acid (D) at amino acid position 52 to be replaced by an alanine (A). 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	0.063
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.0
DANN	Benign	0.74
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.010	N
REVEL	Benign	0.044
Sift	Benign	0.56	T
Sift4G	Benign	0.74	T
Polyphen		0.0030	B
Vest4		0.054
MutPred		0.10		Gain of glycosylation at P53 (P = 0.1057);
MVP		0.048
ClinPred		0.031	T
GERP RS		0.54
Varity_R		0.075
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-84002408;