chr6-24564316-T-C

Variant names:

• chr6-24564316-T-C
• rs2744550
• NM_014809.4:c.2317A>G

Variant summary

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

The NM_014809.4(KIAA0319):​c.2317A>G​(p.Ser773Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,613,302 control chromosomes in the GnomAD database, including 1,214 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 0.050 (421 hom., cov: 32)
  • Exomes 𝑓: 0.023 (793 hom.)
• Consequence: KIAA0319 NM_014809.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 10 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=0.001576066).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.2317A>G	p.Ser773Gly	missense	Exon 15 of 21	NP_055624.2
	KIAA0319	NM_001168375.2		c.2317A>G	p.Ser773Gly	missense	Exon 15 of 21	NP_001161847.1
	KIAA0319	NM_001350403.2		c.2317A>G	p.Ser773Gly	missense	Exon 15 of 21	NP_001337332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.2317A>G	p.Ser773Gly	missense	Exon 15 of 21	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.2317A>G	p.Ser773Gly	missense	Exon 15 of 19	ENSP00000439700.1
	KIAA0319	ENST00000616673.4	TSL:1	c.550A>G	p.Ser184Gly	missense	Exon 11 of 17	ENSP00000483665.1

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7569 AN: 152092 Hom.: 419 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0417

GnomAD2 exomes AF: 0.0209 AC: 5230 AN: 250664 AF XY: 0.0180

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.0126

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.000870

Gnomad FIN exome AF: 0.00333

Gnomad NFE exome AF: 0.0200

Gnomad OTH exome AF: 0.0151

GnomAD4 exome AF: 0.0234 AC: 34210 AN: 1461092 Hom.: 793 Cov.: 31 AF XY: 0.0223 AC XY: 16209 AN XY: 726902

African (AFR) AF: 0.146 AC: 4880 AN: 33396

American (AMR) AF: 0.0132 AC: 591 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26132

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39700

South Asian (SAS) AF: 0.00189 AC: 163 AN: 86256

European-Finnish (FIN) AF: 0.00343 AC: 183 AN: 53420

Middle Eastern (MID) AF: 0.0199 AC: 115 AN: 5766

European-Non Finnish (NFE) AF: 0.0240 AC: 26665 AN: 1111338

Other (OTH) AF: 0.0256 AC: 1546 AN: 60360

GnomAD4 genome AF: 0.0498 AC: 7576 AN: 152210 Hom.: 421 Cov.: 32 AF XY: 0.0468 AC XY: 3481 AN XY: 74430

African (AFR) AF: 0.137 AC: 5671 AN: 41496

American (AMR) AF: 0.0224 AC: 343 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0207 AC: 1409 AN: 68002

Other (OTH) AF: 0.0412 AC: 87 AN: 2110

Alfa AF: 0.0303 Hom.: 432

Bravo AF: 0.0561

TwinsUK AF: 0.0243 AC: 90

ALSPAC AF: 0.0257 AC: 99

ESP6500AA AF: 0.133 AC: 586

ESP6500EA AF: 0.0199 AC: 171

ExAC AF: 0.0230 AC: 2794

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0189

EpiControl AF: 0.0196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.99
DANN	Benign	0.42
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.047	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.18
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.048
Sift	Benign	0.42	T
Sift4G	Benign	0.34	T
Polyphen		0.0010	B
Vest4		0.052
MPC		0.098
ClinPred		0.0084	T
GERP RS		-1.5
Varity_R		0.057
gMVP		0.34
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: rs2744550; hg19: chr6-24564544; COSMIC: COSV107486749;