16-83968768-G-T

Position:

• chr16-83968768-G-T

Variant summary

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

The NM_019065.3(NECAB2):​c.120G>T​(p.Glu40Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 948,426 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: NECAB2 NM_019065.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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=0.030404717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NECAB2	NM_019065.3	c.120G>T	p.Glu40Asp	missense_variant	1/13	ENST00000305202.9
NECAB2	NM_001329748.1	c.120G>T	p.Glu40Asp	missense_variant	1/12
NECAB2	NM_001329749.2	c.-104G>T		5_prime_UTR_variant	1/12
NECAB2	XM_047434240.1	c.-22-3383G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECAB2	ENST00000305202.9	c.120G>T	p.Glu40Asp	missense_variant	1/13	1	NM_019065.3	P1
NECAB2	ENST00000681513.1	n.525G>T		non_coding_transcript_exon_variant	1/13

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000127 AC: 12 AN: 948426 Hom.: 0 Cov.: 31 AF XY: 0.0000157 AC XY: 7 AN XY: 445736

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.0000583

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.6
DANN	Benign	0.96
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.20	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.14	N
REVEL	Benign	0.071
Sift	Benign	0.64	T
Sift4G	Benign	0.55	T
Polyphen		0.10	B
Vest4		0.061
MutPred		0.059		Gain of loop (P = 0.0435);
MVP		0.014
ClinPred		0.049	T
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.052
gMVP		0.17

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: chr16-84002373;