2-23562279-G-A

Position:

• chr2-23562279-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_052920.2(KLHL29):​c.83G>A​(p.Gly28Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KLHL29 NM_052920.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

Genes affected

KLHL29 (HGNC:29404): (kelch like family member 29)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, KLHL29
• BP4: Computational evidence support a benign effect (MetaRNN=0.26360613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL29	NM_052920.2	c.83G>A	p.Gly28Glu	missense_variant	3/14	ENST00000486442.6
KLHL29	XM_006711929.4	c.83G>A	p.Gly28Glu	missense_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL29	ENST00000486442.6	c.83G>A	p.Gly28Glu	missense_variant	3/14	5	NM_052920.2	P1
KLHL29	ENST00000489446.1	n.164G>A		non_coding_transcript_exon_variant	2/4	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 688302

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: 9.28e-7

Gnomad4 OTH exome AF: 0.00

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

Jul 08, 2022

The c.83G>A (p.G28E) alteration is located in exon 3 (coding exon 1) of the KLHL29 gene. This alteration results from a G to A substitution at nucleotide position 83, causing the glycine (G) at amino acid position 28 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	0.27
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	0.93	D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.24
Sift	Uncertain	0.017	D
Sift4G	Benign	0.086	T
Vest4		0.28
MutPred		0.35		Gain of sheet (P = 0.0266);
MVP		0.67
ClinPred		0.69	D
GERP RS		3.8
Varity_R		0.073
gMVP		0.32

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: chr2-23785149;