Variant 9-103004972-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001340.5(CYLC2):c.341T>C(p.Ile114Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,982 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CYLC2
NM_001340.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.22

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.064391434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYLC2	NM_001340.5 linkuse as main transcript	c.341T>C	p.Ile114Thr	missense_variant	5/8	ENST00000374798.8	NP_001331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CYLC2	ENST00000374798.8 linkuse as main transcript	c.341T>C	p.Ile114Thr	missense_variant	5/8	1	NM_001340.5	ENSP00000420256	P1
CYLC2	ENST00000612124.4 linkuse as main transcript	c.341T>C	p.Ile114Thr	missense_variant	5/5	1		ENSP00000478399	P1
CYLC2	ENST00000487798.5 linkuse as main transcript	c.341T>C	p.Ile114Thr	missense_variant	5/7	5		ENSP00000417674	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1426982

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709584

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.341T>C (p.I114T) alteration is located in exon 5 (coding exon 5) of the CYLC2 gene. This alteration results from a T to C substitution at nucleotide position 341, causing the isoleucine (I) at amino acid position 114 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.17

DANN

Benign

0.14

DEOGEN2

Benign

0.0010

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.44

T;.;.

M_CAP

Benign

0.0014

MetaRNN

Benign

0.064

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.18

.;N;N

REVEL

Benign

0.038

Sift

Benign

0.43

.;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.19

B;B;B

Vest4

0.13

MutPred

0.23

Gain of phosphorylation at I114 (P = 0.0059);Gain of phosphorylation at I114 (P = 0.0059);Gain of phosphorylation at I114 (P = 0.0059);

MVP

0.14

MPC

0.0034

ClinPred

0.22

GERP RS

2.6

Varity_R

0.027

gMVP

0.0031

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over