Variant 9-103005363-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001340.5(CYLC2):c.732T>A(p.Asp244Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 1,612,708 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.00046 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 1 hom. )

Consequence

CYLC2
NM_001340.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.19

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.014957398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYLC2	NM_001340.5 linkuse as main transcript	c.732T>A	p.Asp244Glu	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.732T>A	p.Asp244Glu	missense_variant	5/8	1	NM_001340.5	ENSP00000420256	P1
CYLC2	ENST00000612124.4 linkuse as main transcript	c.732T>A	p.Asp244Glu	missense_variant	5/5	1		ENSP00000478399	P1
CYLC2	ENST00000487798.5 linkuse as main transcript	c.732T>A	p.Asp244Glu	missense_variant	5/7	5		ENSP00000417674	P1

Frequencies

GnomAD3 genomes

AF:

0.000458

AC:

AN:

150818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000488

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:

0.0000973

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000959

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.000288

AC:

AN:

250320

Hom.:

AF XY:

0.000251

AC XY:

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000558

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000332

AC:

485

AN:

1461770

Hom.:

Cov.:

AF XY:

0.000358

AC XY:

260

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.000403

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000457

AC:

AN:

150938

Hom.:

Cov.:

AF XY:

0.000584

AC XY:

AN XY:

73658

show subpopulations

Gnomad4 AFR

AF:

0.0000487

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000973

Gnomad4 NFE

AF:

0.000959

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000619

Hom.:

Bravo

AF:

0.000332

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000593

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

Feb 14, 2024

The c.732T>A (p.D244E) alteration is located in exon 5 (coding exon 5) of the CYLC2 gene. This alteration results from a T to A substitution at nucleotide position 732, causing the aspartic acid (D) at amino acid position 244 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.70

DANN

Benign

0.61

DEOGEN2

Benign

0.0053

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.32

T;.;.

M_CAP

Benign

0.0016

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

.;N;N

REVEL

Benign

0.0060

Sift

Benign

0.10

.;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.035

B;B;B

Vest4

0.20

MutPred

0.21

Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);

MVP

0.20

MPC

0.0024

ClinPred

0.024

GERP RS

-0.16

Varity_R

0.047

gMVP

0.000030

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