chr2-169735328-G-A

Variant names:

• chr2-169735328-G-A
• NM_144711.6:c.314G>A

Variant summary

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

The NM_144711.6(KLHL23):​c.314G>A​(p.Arg105Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KLHL23 NM_144711.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81

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=0.23594227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL23	NM_144711.6	c.314G>A	p.Arg105Lys	missense_variant	Exon 2 of 4	ENST00000392647.7	NP_653312.2
PHOSPHO2-KLHL23	NM_001199290.3	c.314G>A	p.Arg105Lys	missense_variant	Exon 4 of 6		NP_001186219.1
PHOSPHO2-KLHL23	NR_144936.2	n.359-6057G>A		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL23	ENST00000392647.7	c.314G>A	p.Arg105Lys	missense_variant	Exon 2 of 4	1	NM_144711.6	ENSP00000376419.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461210 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726798

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.72	.;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.50	N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.28	N;N
REVEL	Benign	0.098
Sift	Benign	0.44	T;T
Sift4G	Benign	0.92	T;T
Polyphen		0.035	B;B
Vest4		0.16
MutPred		0.37		Gain of methylation at R105 (P = 0.0168);Gain of methylation at R105 (P = 0.0168);
MVP		0.72
MPC		0.10
ClinPred		0.40	T
GERP RS		5.8
Varity_R		0.19
gMVP		0.27

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: chr2-170591838;