chr16-83972160-C-G

Variant names:

• chr16-83972160-C-G
• rs768200680
• NM_019065.3:c.211C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019065.3(NECAB2):​c.211C>G​(p.Arg71Gly) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NECAB2 NM_019065.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.878

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.211C>G	p.Arg71Gly	missense	Exon 2 of 13	NP_061938.2
	NECAB2	NM_001329748.1		c.211C>G	p.Arg71Gly	missense	Exon 2 of 12	NP_001316677.1
	NECAB2	NM_001329749.2		c.-13C>G		5_prime_UTR	Exon 2 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.211C>G	p.Arg71Gly	missense	Exon 2 of 13	ENSP00000307449.4	Q7Z6G3-1
	NECAB2	ENST00000565691.5	TSL:1	c.-13C>G		5_prime_UTR	Exon 1 of 11	ENSP00000457354.1	Q7Z6G3-2
	NECAB2	ENST00000933975.1		c.211C>G	p.Arg71Gly	missense	Exon 2 of 13	ENSP00000604034.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.37	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.13	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		1.7
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.2	D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.66		Loss of stability (P = 0.0156)
MVP		0.53
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.76
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs768200680; hg19: chr16-84005765;