Variant 2-201487665-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001168221.2(C2CD6):c.5410T>C(p.Ser1804Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,630 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

C2CD6
NM_001168221.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.294

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012567103).

BP6

Variant 2-201487665-A-G is Benign according to our data. Variant chr2-201487665-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3135974.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD6	NM_001168221.2 link	c.5410T>C	p.Ser1804Pro	missense_variant	16/16	ENST00000439140.6	NP_001161693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
C2CD6	ENST00000439140.6 link	c.5410T>C	p.Ser1804Pro	missense_variant	16/16	1	NM_001168221.2	ENSP00000409937.1	Q53TS8-4
C2CD6	ENST00000286195.7 link	c.1819T>C	p.Ser607Pro	missense_variant	15/15	1		ENSP00000286195.3	Q53TS8-1
C2CD6	ENST00000439802 link	c.*287T>C		3_prime_UTR_variant	13/13	2		ENSP00000400672.1	Q53TS8-2

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000566

AC:

142

AN:

250936

Hom.:

AF XY:

0.000568

AC XY:

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.00126

AC:

1843

AN:

1461382

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

855

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00158

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152248

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000963

Hom.:

Bravo

AF:

0.000714

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000445

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 05, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.11

DANN

Benign

0.74

DEOGEN2

Benign

0.0036

T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.39

T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

2.0

N;N

REVEL

Benign

0.013

Sift

Benign

0.33

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.0010

B;.

Vest4

0.12

MVP

0.014

MPC

0.17

ClinPred

0.0066

GERP RS

-7.5

Varity_R

0.048

gMVP

0.019

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