chr2-169735812-G-T

Position:

• chr2-169735812-G-T

Variant summary

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

The ENST00000392647.7(KLHL23):​c.798G>T​(p.Glu266Asp) 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. 14/20 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: KLHL23 ENST00000392647.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.332

Genes affected

KLHL23 (HGNC:27506): (kelch like family member 23)

PHOSPHO2-KLHL23 (HGNC:):

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=0.11105004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL23	NM_144711.6	c.798G>T	p.Glu266Asp	missense_variant	2/4	ENST00000392647.7	NP_653312.2
PHOSPHO2-KLHL23	NM_001199290.3	c.798G>T	p.Glu266Asp	missense_variant	4/6		NP_001186219.1
PHOSPHO2-KLHL23	NR_144936.2	n.359-5573G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL23	ENST00000392647.7	c.798G>T	p.Glu266Asp	missense_variant	2/4	1	NM_144711.6	ENSP00000376419.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Sep 29, 2023

The c.798G>T (p.E266D) alteration is located in exon 2 (coding exon 1) of the KLHL23 gene. This alteration results from a G to T substitution at nucleotide position 798, causing the glutamic acid (E) at amino acid position 266 to be replaced by an aspartic acid (D). 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	0.067
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T;T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.66	.;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.52	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.93	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.12
MutPred		0.30		Loss of methylation at K265 (P = 0.0862);Loss of methylation at K265 (P = 0.0862);.;
MVP		0.73
MPC		0.091
ClinPred		0.21	T
GERP RS		4.0
Varity_R		0.073
gMVP		0.34

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: chr2-170592322;