KALRN p.Val2205Val

Variant names:

• chr3-124667092-G-G
• NM_001388419.1:c.

Your query was ambiguous. Multiple possible variants found:

• chr3-124667093--
• chr3-124667095-T-C
• chr3-124667095-T-A
• chr3-124667095-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001388419.1(KALRN):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KALRN NM_001388419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.22
• Publications: 0 publications found

Genes affected

KALRN (HGNC:4814): (kalirin RhoGEF kinase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with the huntingtin-associated protein 1, which is a huntingtin binding protein that may function in vesicle trafficking. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388419.1. 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
	KALRN	NM_001388419.1	MANE Select	c.		intron	N/A	NP_001375348.1	O60229-7
	KALRN	NM_001024660.5		c.		intron	N/A	NP_001019831.2	O60229-1
	KALRN	NM_001322988.2		c.		intron	N/A	NP_001309917.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KALRN	ENST00000682506.1	MANE Select	c.		splice_donor intron	N/A	ENSP00000508359.1	O60229-7
	KALRN	ENST00000291478.9	TSL:1	c.		splice_donor intron	N/A	ENSP00000291478.4	O60229-4
	KALRN	ENST00000360013.7	TSL:5	c.		splice_donor intron	N/A	ENSP00000353109.3	O60229-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

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

hg19: chr3-124385939;