rs10221698

Variant names:

• chr2-202074931-T-C
• rs10221698
• NM_001277372.4:c.125T>C

Variant summary

Our verdict is Benign. The variant received -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. 13/17 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
• Publications: 16 publications found

Genes affected

KIAA2012 (HGNC:51250): (KIAA2012)

KIAA2012-AS1 (HGNC:41164): (KIAA2012 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KIAA2012	NM_001277372.4	c.125T>C	p.Val42Ala	missense_variant	Exon 2 of 24	ENST00000498697.3	NP_001264301.2
KIAA2012	NM_001367720.2	c.125T>C	p.Val42Ala	missense_variant	Exon 2 of 24		NP_001354649.1
KIAA2012	XM_017003112.3	c.125T>C	p.Val42Ala	missense_variant	Exon 2 of 13		XP_016858601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA2012	ENST00000498697.3	c.125T>C	p.Val42Ala	missense_variant	Exon 2 of 24	5	NM_001277372.4	ENSP00000419834.2
KIAA2012	ENST00000459709.5	c.125T>C	p.Val42Ala	missense_variant	Exon 2 of 11	2		ENSP00000490419.1
KIAA2012	ENST00000409515.3	n.464T>C		non_coding_transcript_exon_variant	Exon 2 of 15	2
KIAA2012-AS1	ENST00000733168.1	n.234-14098A>G		intron_variant	Intron 1 of 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

GnomAD2 exomes AF: 0.460 AC: 69180 AN: 150526 AF XY: 0.456

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 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

African (AFR) AF: 0.342 AC: 10811 AN: 31572

American (AMR) AF: 0.415 AC: 14788 AN: 35638

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 11147 AN: 25146

East Asian (EAS) AF: 0.176 AC: 6297 AN: 35738

South Asian (SAS) AF: 0.304 AC: 24015 AN: 79094

European-Finnish (FIN) AF: 0.630 AC: 30488 AN: 48358

Middle Eastern (MID) AF: 0.423 AC: 2413 AN: 5700

European-Non Finnish (NFE) AF: 0.560 AC: 603842 AN: 1078906

Other (OTH) AF: 0.481 AC: 27969 AN: 58118

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

African (AFR) AF: 0.340 AC: 14119 AN: 41492

American (AMR) AF: 0.442 AC: 6749 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1064 AN: 5172

South Asian (SAS) AF: 0.278 AC: 1340 AN: 4816

European-Finnish (FIN) AF: 0.638 AC: 6742 AN: 10570

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37907 AN: 67966

Other (OTH) AF: 0.464 AC: 978 AN: 2110

Alfa AF: 0.514 Hom.: 52501

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
PhyloP100		1.1
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
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: rs10221698; hg19: chr2-202939654; COSMIC: COSV55574114;