16-71377688-G-C

Position:

• chr16-71377688-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000302628.9(CALB2):​c.283G>C​(p.Glu95Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CALB2 ENST00000302628.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.22

Genes affected

CALB2 (HGNC:1435): (calbindin 2) This gene encodes an intracellular calcium-binding protein belonging to the troponin C superfamily. Members of this protein family have six EF-hand domains which bind calcium. This protein plays a role in diverse cellular functions, including message targeting and intracellular calcium buffering. It also functions as a modulator of neuronal excitability, and is a diagnostic marker for some human diseases, including Hirschsprung disease and some cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

LINC02136 (HGNC:52995): (long intergenic non-protein coding RNA 2136)

LOC105371332 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALB2	NM_001740.5	c.283G>C	p.Glu95Gln	missense_variant	4/11	ENST00000302628.9	NP_001731.2
LOC105371332	XR_933714.3	n.225-554C>G		intron_variant, non_coding_transcript_variant
CALB2	NM_007088.4	c.283G>C	p.Glu95Gln	missense_variant	4/9		NP_009019.1
CALB2	NR_027910.3	n.353G>C		non_coding_transcript_exon_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALB2	ENST00000302628.9	c.283G>C	p.Glu95Gln	missense_variant	4/11	1	NM_001740.5	ENSP00000307508	P1
LINC02136	ENST00000567469.2	n.625-3106C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Jun 29, 2023

The c.283G>C (p.E95Q) alteration is located in exon 4 (coding exon 4) of the CALB2 gene. This alteration results from a G to C substitution at nucleotide position 283, causing the glutamic acid (E) at amino acid position 95 to be replaced by a glutamine (Q). 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	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.079	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.8	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.3	N;N
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.092	T;T
Polyphen		0.89	P;P
Vest4		0.71
MutPred		0.60		Gain of catalytic residue at E95 (P = 0.0101);Gain of catalytic residue at E95 (P = 0.0101);
MVP		0.93
MPC		0.18
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.35
gMVP		0.62

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-71411591;