chr2-202202454-T-C

Variant names:

• chr2-202202454-T-C
• rs4673235
• NM_001277372.4:c.3433T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001277372.4(KIAA2012):​c.3433T>C​(p.Phe1145Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 399,406 control chromosomes in the GnomAD database, including 196,169 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.98 (73395 hom., cov: 31)
  • Exomes 𝑓: 1.0 (122774 hom.)
• Consequence: KIAA2012 NM_001277372.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57
• Publications: 1 publications found

Genes affected

KIAA2012 (HGNC:51250): (KIAA2012)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039811134).
• BP6: Variant 2-202202454-T-C is Benign according to our data. Variant chr2-202202454-T-C is described in ClinVar as Benign. ClinVar VariationId is 3679303.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277372.4. 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
	KIAA2012	NM_001277372.4	MANE Select	c.3433T>C	p.Phe1145Leu	missense	Exon 23 of 24	NP_001264301.2	H7C5G6
	KIAA2012	NM_001367720.2		c.3430T>C	p.Phe1144Leu	missense	Exon 23 of 24	NP_001354649.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA2012	ENST00000498697.3	TSL:5 MANE Select	c.3433T>C	p.Phe1145Leu	missense	Exon 23 of 24	ENSP00000419834.2	H7C5G6

Frequencies

GnomAD3 genomes AF: 0.981 AC: 149347 AN: 152176 Hom.: 73337 Cov.: 31

Gnomad AFR AF: 0.936

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.987

GnomAD4 exome AF: 0.997 AC: 246310 AN: 247112 Hom.: 122774 Cov.: 0 AF XY: 0.997 AC XY: 124917 AN XY: 125276

African (AFR) AF: 0.932 AC: 6699 AN: 7184

American (AMR) AF: 0.993 AC: 7427 AN: 7476

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 9150 AN: 9236

East Asian (EAS) AF: 1.00 AC: 22894 AN: 22894

South Asian (SAS) AF: 1.00 AC: 3036 AN: 3036

European-Finnish (FIN) AF: 1.00 AC: 21250 AN: 21252

Middle Eastern (MID) AF: 0.995 AC: 1288 AN: 1294

European-Non Finnish (NFE) AF: 1.00 AC: 158286 AN: 158356

Other (OTH) AF: 0.994 AC: 16280 AN: 16384

GnomAD4 genome AF: 0.981 AC: 149464 AN: 152294 Hom.: 73395 Cov.: 31 AF XY: 0.982 AC XY: 73137 AN XY: 74476

African (AFR) AF: 0.936 AC: 38898 AN: 41542

American (AMR) AF: 0.994 AC: 15205 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3439 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 1.00 AC: 4829 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10616 AN: 10616

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 68001 AN: 68042

Other (OTH) AF: 0.987 AC: 2087 AN: 2114

Alfa AF: 0.987 Hom.: 9333

Bravo AF: 0.979

TwinsUK AF: 0.999 AC: 3703

ALSPAC AF: 0.999 AC: 3852

Asia WGS AF: 0.998 AC: 3470 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.65
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0040	T
PhyloP100		1.6
GERP RS		3.9
gMVP		0.020

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4673235; hg19: chr2-203067177;