3-55734892-C-T

Variant names:

• chr3-55734892-C-T
• NM_015576.3:c.2591G>A

Variant summary

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

The NM_015576.3(ERC2):​c.2591G>A​(p.Ser864Asn) 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: 32)
• Consequence: ERC2 NM_015576.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

ERC2 (HGNC:31922): (ELKS/RAB6-interacting/CAST family member 2) This gene encodes a protein that belongs to the Rab3-interacting molecule (RIM)-binding protein family. Members of this protein family form part of the cytomatrix at the active zone (CAZ) complex and function as regulators of neurotransmitter release. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

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 rank	MANE	Protein	UniProt
ERC2	NM_015576.3	c.2591G>A	p.Ser864Asn	missense_variant	Exon 15 of 18	ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.2591G>A	p.Ser864Asn	missense_variant	Exon 15 of 18	1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.2591G>A		non_coding_transcript_exon_variant	Exon 15 of 19	1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.2615G>A	p.Ser872Asn	missense_variant	Exon 15 of 18	5		ENSP00000417280.3
ERC2	ENST00000487287.1	n.139G>A		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2591G>A (p.S864N) alteration is located in exon 15 (coding exon 14) of the ERC2 gene. This alteration results from a G to A substitution at nucleotide position 2591, causing the serine (S) at amino acid position 864 to be replaced by an asparagine (N). 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	0.98
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	.;D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.6	N;.
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;.
Sift4G	Benign	0.18	T;T
Polyphen		0.98	D;D
Vest4		0.70
MutPred		0.51		Loss of phosphorylation at S864 (P = 0.0436);Loss of phosphorylation at S864 (P = 0.0436);
MVP		0.40
MPC		1.1
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.65
gMVP		0.62

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: chr3-55768920;