chr6-24570116-A-T

Variant names:

• chr6-24570116-A-T
• rs2817195
• NM_014809.4:c.1859-81T>A

Variant summary

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

The NM_014809.4(KIAA0319):​c.1859-81T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000082 in 1,219,892 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: not found (cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 0 publications found

Genes affected

KIAA0319 (HGNC:21580): (KIAA0319) This gene encodes a transmembrane protein that contains a large extracellular domain with multiple polycystic kidney disease (PKD) domains. The encoded protein may play a role in the development of the cerebral cortex by regulating neuronal migration and cell adhesion. Single nucleotide polymorphisms in this gene are associated with dyslexia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

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=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014809.4. 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
	KIAA0319	NM_014809.4	MANE Select	c.1859-81T>A		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.1859-81T>A		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.1859-81T>A		intron	N/A	NP_001337332.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.1859-81T>A		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.1859-81T>A		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000616673.4	TSL:1	c.92-81T>A		intron	N/A	ENSP00000483665.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.20e-7 AC: 1 AN: 1219892 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 607892

African (AFR) AF: 0.00 AC: 0 AN: 28570

American (AMR) AF: 0.00 AC: 0 AN: 36168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22026

East Asian (EAS) AF: 0.00 AC: 0 AN: 36932

South Asian (SAS) AF: 0.00 AC: 0 AN: 72334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3704

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 921250

Other (OTH) AF: 0.00 AC: 0 AN: 51656

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.83
PhyloP100		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2817195; hg19: chr6-24570344;