chr9-103005359-A-G

Position:

• chr9-103005359-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001340.5(CYLC2):​c.728A>G​(p.Lys243Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: CYLC2 NM_001340.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.890

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15542206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYLC2	NM_001340.5	c.728A>G	p.Lys243Arg	missense_variant	5/8	ENST00000374798.8	NP_001331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYLC2	ENST00000374798.8	c.728A>G	p.Lys243Arg	missense_variant	5/8	1	NM_001340.5	ENSP00000420256.1
CYLC2	ENST00000612124.4	c.728A>G	p.Lys243Arg	missense_variant	5/5	1		ENSP00000478399.1
CYLC2	ENST00000487798.5	c.728A>G	p.Lys243Arg	missense_variant	5/7	5		ENSP00000417674.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

The c.728A>G (p.K243R) alteration is located in exon 5 (coding exon 5) of the CYLC2 gene. This alteration results from a A to G substitution at nucleotide position 728, causing the lysine (K) at amino acid position 243 to be replaced by an arginine (R). 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	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.041	T;T;T
Eigen	Benign	0.068
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.43	T;.;.
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	.;N;N
REVEL	Benign	0.074
Sift	Benign	0.16	.;T;T
Sift4G	Uncertain	0.014	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.12
MutPred		0.20		Loss of ubiquitination at K243 (P = 0.0233);Loss of ubiquitination at K243 (P = 0.0233);Loss of ubiquitination at K243 (P = 0.0233);
MVP		0.43
MPC		0.0026
ClinPred		0.80	D
GERP RS		3.4
Varity_R		0.043
gMVP		0.00014

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.

Other links and lift over

hg19: chr9-105767641;