rs2114646

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-169767711-C-A
• chr2-169767711-C-G
• chr2-169767711-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000448589.1(KLHL23):​c.44-8730C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 374,500 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

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>A		intron	N/A	ENSP00000394732.1	H7C0F4
	KLHL23	ENST00000448589.1	TSL:2	c.44-8730C>A		intron	N/A	ENSP00000400833.1	H7C1K9
	PTCHD3P2	ENST00000424937.1	TSL:6	n.1087+2G>T		splice_donor intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151974 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000225 AC: 5 AN: 222526 Hom.: 0 Cov.: 0 AF XY: 0.0000158 AC XY: 2 AN XY: 126682

African (AFR) AF: 0.000151 AC: 1 AN: 6624

American (AMR) AF: 0.00 AC: 0 AN: 20828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4650

East Asian (EAS) AF: 0.00 AC: 0 AN: 9912

South Asian (SAS) AF: 0.00 AC: 0 AN: 37526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1964

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 120068

Other (OTH) AF: 0.000388 AC: 4 AN: 10314

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151974 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74192

African (AFR) AF: 0.0000242 AC: 1 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 4612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.85
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;