rs2744564

Variant names:

• chr6-24579985-C-G
• rs2744564
• NM_014809.4:c.1280-35G>C

Variant summary

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

The NM_014809.4(KIAA0319):​c.1280-35G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,462,394 control chromosomes in the GnomAD database, including 2,171 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 0.072 (935 hom., cov: 31)
  • Exomes 𝑓: 0.028 (1236 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

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.1280-35G>C		intron	N/A	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.1280-35G>C		intron	N/A	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.1280-35G>C		intron	N/A	NP_001337332.1	Q5VV43-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.1280-35G>C		intron	N/A	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.1280-35G>C		intron	N/A	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000616673.4	TSL:1	c.-449-35G>C		intron	N/A	ENSP00000483665.1	A0A087X0U9

Frequencies

GnomAD3 genomes AF: 0.0714 AC: 10860 AN: 152024 Hom.: 930 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0589

GnomAD2 exomes AF: 0.0264 AC: 4449 AN: 168250 AF XY: 0.0218

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.0190

Gnomad ASJ exome AF: 0.00612

Gnomad EAS exome AF: 0.000965

Gnomad FIN exome AF: 0.00349

Gnomad NFE exome AF: 0.0231

Gnomad OTH exome AF: 0.0203

GnomAD4 exome AF: 0.0276 AC: 36176 AN: 1310252 Hom.: 1236 Cov.: 19 AF XY: 0.0261 AC XY: 17015 AN XY: 652432

African (AFR) AF: 0.226 AC: 6823 AN: 30254

American (AMR) AF: 0.0201 AC: 741 AN: 36922

Ashkenazi Jewish (ASJ) AF: 0.00683 AC: 168 AN: 24584

East Asian (EAS) AF: 0.000467 AC: 17 AN: 36418

South Asian (SAS) AF: 0.00241 AC: 187 AN: 77716

European-Finnish (FIN) AF: 0.00332 AC: 166 AN: 50060

Middle Eastern (MID) AF: 0.0257 AC: 142 AN: 5522

European-Non Finnish (NFE) AF: 0.0263 AC: 26088 AN: 993690

Other (OTH) AF: 0.0335 AC: 1844 AN: 55086

GnomAD4 genome AF: 0.0716 AC: 10897 AN: 152142 Hom.: 935 Cov.: 31 AF XY: 0.0684 AC XY: 5091 AN XY: 74394

African (AFR) AF: 0.210 AC: 8703 AN: 41462

American (AMR) AF: 0.0323 AC: 494 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4826

European-Finnish (FIN) AF: 0.00321 AC: 34 AN: 10606

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1487 AN: 67988

Other (OTH) AF: 0.0583 AC: 123 AN: 2110

Alfa AF: 0.0410 Hom.: 82

Bravo AF: 0.0811

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.029
DANN	Benign	0.32
PhyloP100		-1.3
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: rs2744564; hg19: chr6-24580213;