2-169767711-C-T

Variant names:

• chr2-169767711-C-T
• rs2114646
• ENST00000437875.1:c.830-5609C>T

Variant summary

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

The ENST00000448589.1(KLHL23):​c.44-8730C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 373,276 control chromosomes in the GnomAD database, including 12,789 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 0.20 (3991 hom., cov: 32)
  • Exomes 𝑓: 0.25 (8798 hom.)
• Consequence: KLHL23 ENST00000448589.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 11 publications found

Genes affected

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

PTCHD3P2 (HGNC:44946): (patched domain containing 3 pseudogene 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448589.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL23	ENST00000437875.1	TSL:3	c.830-5609C>T		intron	N/A	ENSP00000394732.1	H7C0F4
	KLHL23	ENST00000448589.1	TSL:2	c.44-8730C>T		intron	N/A	ENSP00000400833.1	H7C1K9
	PTCHD3P2	ENST00000424937.1	TSL:6	n.1087+2G>A		splice_donor intron	N/A

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30277 AN: 151926 Hom.: 3979 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.255 AC: 56323 AN: 221232 Hom.: 8798 Cov.: 0 AF XY: 0.252 AC XY: 31720 AN XY: 125936

African (AFR) AF: 0.0518 AC: 343 AN: 6616

American (AMR) AF: 0.507 AC: 10472 AN: 20640

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 699 AN: 4630

East Asian (EAS) AF: 0.413 AC: 4047 AN: 9804

South Asian (SAS) AF: 0.294 AC: 10968 AN: 37308

European-Finnish (FIN) AF: 0.245 AC: 2584 AN: 10558

Middle Eastern (MID) AF: 0.133 AC: 261 AN: 1962

European-Non Finnish (NFE) AF: 0.207 AC: 24713 AN: 119448

Other (OTH) AF: 0.218 AC: 2236 AN: 10266

GnomAD4 genome AF: 0.199 AC: 30299 AN: 152044 Hom.: 3991 Cov.: 32 AF XY: 0.208 AC XY: 15456 AN XY: 74300

African (AFR) AF: 0.0548 AC: 2274 AN: 41516

American (AMR) AF: 0.354 AC: 5404 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2099 AN: 5160

South Asian (SAS) AF: 0.319 AC: 1532 AN: 4806

European-Finnish (FIN) AF: 0.284 AC: 2997 AN: 10550

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.218 AC: 14788 AN: 67962

Other (OTH) AF: 0.186 AC: 392 AN: 2108

Alfa AF: 0.207 Hom.: 4612

Bravo AF: 0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2114646;

hg19: chr2-170624221;