chr2-23646777-G-A

Variant names:

• chr2-23646777-G-A
• rs535200
• NM_052920.2:c.940+3927G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052920.2(KLHL29):​c.940+3927G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,198 control chromosomes in the GnomAD database, including 2,268 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (2268 hom., cov: 33)
• Consequence: KLHL29 NM_052920.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL29	NM_052920.2	c.940+3927G>A		intron_variant	Intron 5 of 13	ENST00000486442.6	NP_443152.1
KLHL29	XM_006711929.4	c.940+3927G>A		intron_variant	Intron 4 of 12		XP_006711992.1
KLHL29	XM_011532501.3	c.22+1673G>A		intron_variant	Intron 2 of 10		XP_011530803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL29	ENST00000486442.6	c.940+3927G>A		intron_variant	Intron 5 of 13	5	NM_052920.2	ENSP00000420659.1
KLHL29	ENST00000288548.5	c.457+3927G>A		intron_variant	Intron 1 of 6	1		ENSP00000288548.5

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17235 AN: 152080 Hom.: 2247 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0144

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0895

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17303 AN: 152198 Hom.: 2268 Cov.: 33 AF XY: 0.111 AC XY: 8236 AN XY: 74432

African (AFR) AF: 0.321 AC: 13307 AN: 41478

American (AMR) AF: 0.0578 AC: 884 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 168 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5176

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4826

European-Finnish (FIN) AF: 0.0144 AC: 153 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0352 AC: 2391 AN: 68022

Other (OTH) AF: 0.0885 AC: 187 AN: 2112

Alfa AF: 0.0654 Hom.: 585

Bravo AF: 0.125

Asia WGS AF: 0.0460 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.69
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs535200; hg19: chr2-23869647;