chr16-83968713-A-C

Variant names:

• chr16-83968713-A-C
• NM_019065.3:c.65A>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.65A>C​(p.Gln22Pro) 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: -0.0580

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=0.02922818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECAB2	NM_019065.3	c.65A>C	p.Gln22Pro	missense_variant	Exon 1 of 13	ENST00000305202.9	NP_061938.2
NECAB2	NM_001329748.1	c.65A>C	p.Gln22Pro	missense_variant	Exon 1 of 12		NP_001316677.1
NECAB2	NM_001329749.2	c.-159A>C		5_prime_UTR_variant	Exon 1 of 12		NP_001316678.1
NECAB2	XM_047434240.1	c.-22-3438A>C		intron_variant	Intron 1 of 11		XP_047290196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECAB2	ENST00000305202.9	c.65A>C	p.Gln22Pro	missense_variant	Exon 1 of 13	1	NM_019065.3	ENSP00000307449.4
NECAB2	ENST00000681513.1	n.470A>C		non_coding_transcript_exon_variant	Exon 1 of 13

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.65A>C (p.Q22P) 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 65, causing the glutamine (Q) at amino acid position 22 to be replaced by a proline (P). 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	0.039
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.3
DANN	Benign	0.68
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.55	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.40	N
REVEL	Benign	0.025
Sift	Benign	1.0	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.091
MutPred		0.17		Gain of loop (P = 0.0121);
MVP		0.030
ClinPred		0.026	T
GERP RS		0.38
Varity_R		0.12
gMVP		0.34

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: chr16-84002318;