rs2744559

Variant names:

• chr6-24576403-C-T
• rs2744559
• NM_014809.4:c.1699G>A

Variant summary

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

The NM_014809.4(KIAA0319):​c.1699G>A​(p.Gly567Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0318 in 1,613,952 control chromosomes in the GnomAD database, including 2,527 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.077 (1105 hom., cov: 32)
  • Exomes 𝑓: 0.027 (1422 hom.)
• Consequence: KIAA0319 NM_014809.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.15
• Publications: 12 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 (MetaRNN=0.0015474856).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 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.1699G>A	p.Gly567Ser	missense	Exon 10 of 21	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.1699G>A	p.Gly567Ser	missense	Exon 10 of 21	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.1699G>A	p.Gly567Ser	missense	Exon 10 of 21	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.1699G>A	p.Gly567Ser	missense	Exon 10 of 21	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.1699G>A	p.Gly567Ser	missense	Exon 10 of 19	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000616673.4	TSL:1	c.-30G>A		5_prime_UTR	Exon 6 of 17	ENSP00000483665.1	A0A087X0U9

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11742 AN: 152006 Hom.: 1099 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00302

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0218

Gnomad OTH AF: 0.0617

GnomAD2 exomes AF: 0.0287 AC: 7221 AN: 251360 AF XY: 0.0237

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.0197

Gnomad ASJ exome AF: 0.00635

Gnomad EAS exome AF: 0.000870

Gnomad FIN exome AF: 0.00319

Gnomad NFE exome AF: 0.0210

Gnomad OTH exome AF: 0.0205

GnomAD4 exome AF: 0.0271 AC: 39611 AN: 1461828 Hom.: 1422 Cov.: 31 AF XY: 0.0255 AC XY: 18573 AN XY: 727228

African (AFR) AF: 0.239 AC: 7990 AN: 33472

American (AMR) AF: 0.0205 AC: 917 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00696 AC: 182 AN: 26136

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39700

South Asian (SAS) AF: 0.00240 AC: 207 AN: 86258

European-Finnish (FIN) AF: 0.00314 AC: 168 AN: 53420

Middle Eastern (MID) AF: 0.0246 AC: 142 AN: 5766

European-Non Finnish (NFE) AF: 0.0251 AC: 27953 AN: 1111960

Other (OTH) AF: 0.0336 AC: 2028 AN: 60392

GnomAD4 genome AF: 0.0774 AC: 11779 AN: 152124 Hom.: 1105 Cov.: 32 AF XY: 0.0741 AC XY: 5514 AN XY: 74366

African (AFR) AF: 0.231 AC: 9553 AN: 41444

American (AMR) AF: 0.0346 AC: 529 AN: 15280

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

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4818

European-Finnish (FIN) AF: 0.00302 AC: 32 AN: 10596

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0218 AC: 1481 AN: 68016

Other (OTH) AF: 0.0611 AC: 129 AN: 2112

Alfa AF: 0.0407 Hom.: 1030

Bravo AF: 0.0877

TwinsUK AF: 0.0259 AC: 96

ALSPAC AF: 0.0270 AC: 104

ESP6500AA AF: 0.225 AC: 991

ESP6500EA AF: 0.0210 AC: 181

ExAC AF: 0.0326 AC: 3960

Asia WGS AF: 0.0170 AC: 59 AN: 3478

EpiCase AF: 0.0198

EpiControl AF: 0.0204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.18
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.47	N
PhyloP100		4.1
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.62	N
REVEL	Benign	0.076
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.027	B
Vest4		0.055
MPC		0.12
ClinPred		0.015	T
GERP RS		3.0
Varity_R		0.091
gMVP		0.30
Mutation Taster		=98/2	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: rs2744559; hg19: chr6-24576631; COSMIC: COSV107486750;