16-83968803-A-C

Variant names:

• chr16-83968803-A-C
• NM_019065.3:c.155A>C

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019065.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECAB2	NM_019065.3	MANE Select	c.155A>C	p.Asp52Ala	missense	Exon 1 of 13	NP_061938.2
	NECAB2	NM_001329748.1		c.155A>C	p.Asp52Ala	missense	Exon 1 of 12	NP_001316677.1
	NECAB2	NM_001329749.2		c.-69A>C		5_prime_UTR	Exon 1 of 12	NP_001316678.1	Q7Z6G3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECAB2	ENST00000305202.9	TSL:1 MANE Select	c.155A>C	p.Asp52Ala	missense	Exon 1 of 13	ENSP00000307449.4	Q7Z6G3-1
	NECAB2	ENST00000933975.1		c.155A>C	p.Asp52Ala	missense	Exon 1 of 13	ENSP00000604034.1
	NECAB2	ENST00000933977.1		c.155A>C	p.Asp52Ala	missense	Exon 1 of 11	ENSP00000604036.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-2.0
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

Other links and lift over

hg19: chr16-84002408;