2-200490171-T-G

Position:

• chr2-200490171-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152387.4(KCTD18):​c.1210A>C​(p.Lys404Gln) 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. 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: 33)
• Consequence: KCTD18 NM_152387.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.407

Genes affected

KCTD18 (HGNC:26446): (potassium channel tetramerization domain containing 18) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.03577757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD18	NM_152387.4	c.1210A>C	p.Lys404Gln	missense_variant	7/7	ENST00000359878.8	NP_689600.2
KCTD18	NM_001321547.2	c.1210A>C	p.Lys404Gln	missense_variant	7/7		NP_001308476.1
KCTD18	NM_001321548.2	c.583A>C	p.Lys195Gln	missense_variant	7/7		NP_001308477.1
KCTD18	NM_001321550.2	c.583A>C	p.Lys195Gln	missense_variant	7/7		NP_001308479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD18	ENST00000359878.8	c.1210A>C	p.Lys404Gln	missense_variant	7/7	1	NM_152387.4	ENSP00000352941	P1
KCTD18	ENST00000409157.5	c.1210A>C	p.Lys404Gln	missense_variant	7/7	1		ENSP00000386751	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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

Mar 31, 2024

The c.1210A>C (p.K404Q) alteration is located in exon 7 (coding exon 6) of the KCTD18 gene. This alteration results from a A to C substitution at nucleotide position 1210, causing the lysine (K) at amino acid position 404 to be replaced by a glutamine (Q). 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	0.066
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.27
DANN	Benign	0.23
DEOGEN2	Benign	0.0011	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.41	.;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.1	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.14	N;N
REVEL	Benign	0.0060
Sift	Benign	0.78	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.0	B;B
Vest4		0.025
MutPred		0.21		Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);
MVP		0.18
MPC		0.21
ClinPred		0.023	T
GERP RS		-3.0
Varity_R		0.032
gMVP		0.13

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: chr2-201354894;