chr3-55992160-C-G

Variant names:

• chr3-55992160-C-G
• rs751851932
• NM_015576.3:c.2152G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015576.3(ERC2):​c.2152G>C​(p.Glu718Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. E718K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERC2 NM_015576.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 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.2152G>C	p.Glu718Gln	missense_variant	Exon 11 of 18	ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.2152G>C	p.Glu718Gln	missense_variant	Exon 11 of 18	1	NM_015576.3	ENSP00000288221.6
ERC2	ENST00000460849.5	n.2152G>C		non_coding_transcript_exon_variant	Exon 11 of 19	1		ENSP00000417445.1
ERC2	ENST00000492584.3	c.2188G>C	p.Glu730Gln	missense_variant	Exon 12 of 18	5		ENSP00000417280.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	.;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.0	M;M
PhyloP100		7.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.18
Sift	Benign	0.16	T;.
Sift4G	Uncertain	0.013	D;D
Polyphen		0.94	P;P
Vest4		0.65
MutPred		0.62		Loss of ubiquitination at K721 (P = 0.1154);Loss of ubiquitination at K721 (P = 0.1154);
MVP		0.30
MPC		1.1
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.21
gMVP		0.64
Mutation Taster		=78/22	polymorphism

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: rs751851932; hg19: chr3-56026188;