rs2243831

Variant names:

• chr6-24554534-T-C
• rs2243831
• NM_014809.4:c.2948+7A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-24554534-T-C
• chr6-24554534-T-A
• chr6-24554534-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_014809.4(KIAA0319):​c.2948+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,602,474 control chromosomes in the GnomAD database, including 49,458 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.29 (7878 hom., cov: 32)
  • Exomes 𝑓: 0.23 (41580 hom.)
• Consequence: KIAA0319 NM_014809.4 splice_region, intron
• Scores: Splicing: ADA: 0.00009128
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.517
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-24554534-T-C is Benign according to our data. Variant chr6-24554534-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060264.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 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.2948+7A>G		splice_region intron	N/A	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.2948+7A>G		splice_region intron	N/A	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.2948+7A>G		splice_region 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.2948+7A>G		splice_region intron	N/A	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.2857+2073A>G		intron	N/A	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000616673.4	TSL:1	c.1181+7A>G		splice_region intron	N/A	ENSP00000483665.1	A0A087X0U9

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44619 AN: 151992 Hom.: 7858 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.279

GnomAD2 exomes AF: 0.225 AC: 56430 AN: 251072 AF XY: 0.223

Gnomad AFR exome AF: 0.499

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.105

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.232 AC: 336492 AN: 1450364 Hom.: 41580 Cov.: 29 AF XY: 0.231 AC XY: 166962 AN XY: 722298

African (AFR) AF: 0.510 AC: 16902 AN: 33128

American (AMR) AF: 0.160 AC: 7140 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 5456 AN: 26058

East Asian (EAS) AF: 0.106 AC: 4189 AN: 39652

South Asian (SAS) AF: 0.237 AC: 20409 AN: 86002

European-Finnish (FIN) AF: 0.257 AC: 13682 AN: 53316

Middle Eastern (MID) AF: 0.312 AC: 1793 AN: 5750

European-Non Finnish (NFE) AF: 0.229 AC: 252708 AN: 1101746

Other (OTH) AF: 0.237 AC: 14213 AN: 60010

GnomAD4 genome AF: 0.294 AC: 44674 AN: 152110 Hom.: 7878 Cov.: 32 AF XY: 0.291 AC XY: 21647 AN XY: 74396

African (AFR) AF: 0.496 AC: 20575 AN: 41458

American (AMR) AF: 0.204 AC: 3120 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3468

East Asian (EAS) AF: 0.110 AC: 570 AN: 5186

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4818

European-Finnish (FIN) AF: 0.258 AC: 2734 AN: 10590

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.222 AC: 15098 AN: 67988

Other (OTH) AF: 0.276 AC: 583 AN: 2114

Alfa AF: 0.242 Hom.: 22583

Bravo AF: 0.299

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	KIAA0319-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.64
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000091
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.030		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: rs2243831; hg19: chr6-24554762; COSMIC: COSV65497109;