NM_001008220.2:c.308C>A

Variant names:

• chr5-175879948-C-A
• rs760771461
• NM_001008220.2:c.308C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001008220.2(CPLX2):​c.308C>A​(p.Ala103Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. A103V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: CPLX2 NM_001008220.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.22
• Publications: 1 publications found

Genes affected

CPLX2 (HGNC:2310): (complexin 2) Proteins encoded by the complexin/synaphin gene family are cytosolic proteins that function in synaptic vesicle exocytosis. These proteins bind syntaxin, part of the SNAP receptor. The protein product of this gene binds to the SNAP receptor complex and disrupts it, allowing transmitter release. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09710398).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008220.2. 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
	CPLX2	NM_001008220.2	MANE Select	c.308C>A	p.Ala103Glu	missense	Exon 4 of 4	NP_001008221.1	Q6PUV4
	CPLX2	NM_006650.4		c.308C>A	p.Ala103Glu	missense	Exon 5 of 5	NP_006641.1	Q6PUV4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPLX2	ENST00000393745.8	TSL:1 MANE Select	c.308C>A	p.Ala103Glu	missense	Exon 4 of 4	ENSP00000377346.3	Q6PUV4
	CPLX2	ENST00000359546.8	TSL:1	c.308C>A	p.Ala103Glu	missense	Exon 5 of 5	ENSP00000352544.4	Q6PUV4
	CPLX2	ENST00000515094.1	TSL:4	c.308C>A	p.Ala103Glu	missense	Exon 4 of 4	ENSP00000421825.1	Q6PUV4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000799 AC: 2 AN: 250160 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461672 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 727090

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111934

Other (OTH) AF: 0.0000497 AC: 3 AN: 60376

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000868 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		6.2
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.022	B
Vest4		0.26
MutPred		0.28		Gain of solvent accessibility (P = 0.0456)
MVP		0.15
MPC		1.1
ClinPred		0.14	T
GERP RS		4.3
Varity_R		0.087
gMVP		0.74
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs760771461; hg19: chr5-175306951;