rs10221698

Positions:

• chr2-202074931-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001277372.4(KIAA2012):​c.125T>C​(p.Val42Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,550,344 control chromosomes in the GnomAD database, including 215,473 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 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 0.47 (17757 hom., cov: 32)
  • Exomes 𝑓: 0.52 (197716 hom.)
• Consequence: KIAA2012 NM_001277372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

Genes affected

KIAA2012 (HGNC:51250): (KIAA2012)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.270892E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA2012	NM_001277372.4	c.125T>C	p.Val42Ala	missense_variant	2/24	ENST00000498697.3
KIAA2012	NM_001367720.2	c.125T>C	p.Val42Ala	missense_variant	2/24
KIAA2012	XM_017003112.3	c.125T>C	p.Val42Ala	missense_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA2012	ENST00000498697.3	c.125T>C	p.Val42Ala	missense_variant	2/24	5	NM_001277372.4	P1
KIAA2012	ENST00000459709.5	c.125T>C	p.Val42Ala	missense_variant	2/11	2
KIAA2012	ENST00000409515.3	n.464T>C		non_coding_transcript_exon_variant	2/15	2

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70956 AN: 151956 Hom.: 17753 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.463

GnomAD3 exomes AF: 0.460 AC: 69180 AN: 150526 Hom.: 17211 AF XY: 0.456 AC XY: 36778 AN XY: 80600

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.411

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.217

Gnomad SAS exome AF: 0.296

Gnomad FIN exome AF: 0.631

Gnomad NFE exome AF: 0.558

Gnomad OTH exome AF: 0.476

GnomAD4 exome AF: 0.523 AC: 731770 AN: 1398270 Hom.: 197716 Cov.: 52 AF XY: 0.518 AC XY: 357073 AN XY: 689616

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.415

Gnomad4 ASJ exome AF: 0.443

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.304

Gnomad4 FIN exome AF: 0.630

Gnomad4 NFE exome AF: 0.560

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.467 AC: 70976 AN: 152074 Hom.: 17757 Cov.: 32 AF XY: 0.466 AC XY: 34633 AN XY: 74324

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.464

Alfa AF: 0.514 Hom.: 21983

Bravo AF: 0.448

TwinsUK AF: 0.574 AC: 2127

ALSPAC AF: 0.557 AC: 2148

ExAC AF: 0.401 AC: 8118

Asia WGS AF: 0.286 AC: 993 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.1
DANN	Benign	0.67
DEOGEN2	Benign	0.011	.;T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.44	T;T;T
MetaRNN	Benign	0.000033	T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	.;N;.
REVEL	Benign	0.065
Sift	Benign	0.32	.;T;.
Sift4G	Benign	0.21	.;T;.
Vest4		0.044
ClinPred		0.0080	T
GERP RS		0.89
Varity_R		0.022
gMVP		0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs10221698; hg19: chr2-202939654; COSMIC: COSV55574114;