Variant 9-103003183-G-T 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_001340.5(CYLC2):c.100G>T(p.Ala34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

CYLC2
NM_001340.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.313

Variant links:

Genes affected

CYLC2 (HGNC:2583): (cylicin 2) Cylicin II (CYCL2) is specifically expressed in testis and is part of the cytoskeletal calyx of mammalian sperm heads. Cylicin II may play a role in the morphogenesis of the sperm head. [provided by RefSeq, Jul 2008]

CYLC2 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=0.05210817).

BP6

Variant 9-103003183-G-T is Benign according to our data. Variant chr9-103003183-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2283423.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYLC2	NM_001340.5 linkuse as main transcript	c.100G>T	p.Ala34Ser	missense_variant	3/8	ENST00000374798.8	NP_001331.1	Q14093A0A024R146Q6PEJ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CYLC2	ENST00000374798.8 linkuse as main transcript	c.100G>T	p.Ala34Ser	missense_variant	3/8	1	NM_001340.5	ENSP00000420256.1	Q14093
CYLC2	ENST00000612124.4 linkuse as main transcript	c.100G>T	p.Ala34Ser	missense_variant	3/5	1		ENSP00000478399.1	Q14093
CYLC2	ENST00000487798.5 linkuse as main transcript	c.100G>T	p.Ala34Ser	missense_variant	3/7	5		ENSP00000417674.1	Q14093

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251360

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461488

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000112

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.000410

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000441

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000247

AC:

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

Apr 12, 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

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.0069

T;T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.66

T;.;.

M_CAP

Benign

0.0038

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.86

L;L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.59

.;N;N

REVEL

Benign

0.044

Sift

Benign

0.64

.;T;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.39

B;B;B

Vest4

0.24

MutPred

0.41

Gain of disorder (P = 0.0084);Gain of disorder (P = 0.0084);Gain of disorder (P = 0.0084);

MVP

0.040

MPC

0.0040

ClinPred

0.073

GERP RS

-4.7

Varity_R

0.039

gMVP

0.021

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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