Variant 2-201492363-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001168221.2(C2CD6):c.3978G>C(p.Gln1326His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,534,982 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 10 hom., cov: 32)

Exomes 𝑓: 0.011 ( 89 hom. )

Consequence

C2CD6
NM_001168221.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.210

Variant links:

Genes affected

C2CD6 (HGNC:14438): (C2 calcium dependent domain containing 6) An autosomal recessive form of juvenile amyotrophic lateral sclerosis was originally mapped to a region of chromosome 2 that includes this gene. The encoded protein contains a calcium-dependent membrane targeting C2 domain. This domain is often found in proteins that are involved in membrane trafficking and signal transduction. [provided by RefSeq, Jun 2016]

C2CD6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, C2CD6

BP4

Computational evidence support a benign effect (MetaRNN=0.0041075945).

BP6

Variant 2-201492363-C-G is Benign according to our data. Variant chr2-201492363-C-G is described in ClinVar as [Benign]. Clinvar id is 2651818.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C2CD6	NM_001168221.2 linkuse as main transcript	c.3978G>C	p.Gln1326His	missense_variant	15/16	ENST00000439140.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C2CD6	ENST00000439140.6 linkuse as main transcript	c.3978G>C	p.Gln1326His	missense_variant	15/16	1	NM_001168221.2	A2	Q53TS8-4
C2CD6	ENST00000286195.7 linkuse as main transcript	c.1581+3532G>C		intron_variant		1		P2	Q53TS8-1
C2CD6	ENST00000439802.5 linkuse as main transcript	c.*49+3532G>C		intron_variant		2			Q53TS8-2
C2CD6	ENST00000482942.1 linkuse as main transcript	n.101-4461G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00932

AC:

1417

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0139

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00834

AC:

1164

AN:

139566

Hom.:

AF XY:

0.00840

AC XY:

631

AN XY:

75102

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00514

Gnomad ASJ exome

AF:

0.00815

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00366

Gnomad FIN exome

AF:

0.0223

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.00950

GnomAD4 exome

AF:

0.0106

AC:

14609

AN:

1382802

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

7300

AN XY:

682400

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00544

Gnomad4 ASJ exome

AF:

0.00832

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00389

Gnomad4 FIN exome

AF:

0.0197

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.00861

GnomAD4 genome

AF:

0.00931

AC:

1417

AN:

152180

Hom.:

Cov.:

AF XY:

0.00945

AC XY:

703

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00713

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0208

Gnomad4 NFE

AF:

0.0139

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00843

Hom.:

Bravo

AF:

0.00742

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0101

AC:

ExAC

AF:

0.00731

AC:

158

Asia WGS

AF:

0.00145

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

C2CD6: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.052

Sift

Pathogenic

0.0

Sift4G

Benign

0.27

Vest4

0.47

MutPred

0.23

Gain of catalytic residue at L1328 (P = 0.0676);

MVP

0.38

MPC

0.59

ClinPred

0.043

GERP RS

2.4

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over