2-202202454-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 5/7 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

Genes affected

KIAA2012 (HGNC:51250): (KIAA2012)

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA2012	NM_001277372.4	c.3433T>C	p.Phe1145Leu	missense_variant	Exon 23 of 24	ENST00000498697.3	NP_001264301.2
KIAA2012	NM_001367720.2	c.3430T>C	p.Phe1144Leu	missense_variant	Exon 23 of 24		NP_001354649.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA2012	ENST00000498697.3	c.3433T>C	p.Phe1145Leu	missense_variant	Exon 23 of 24	5	NM_001277372.4	ENSP00000419834.2

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

Gnomad4 AFR exome AF: 0.932

Gnomad4 AMR exome AF: 0.993

Gnomad4 ASJ exome AF: 0.991

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.994

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

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.994

Gnomad4 ASJ AF: 0.992

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.987

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
GERP RS		3.9
gMVP		0.020

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4673235; hg19: chr2-203067177;