2-202202454-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001277372.4(KIAA2012):​c.3433T>G​(p.Phe1145Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F1145L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIAA2012 NM_001277372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 1 publications found

Genes affected

KIAA2012 (HGNC:51250): (KIAA2012)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20444435).

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>G	p.Phe1145Val	missense	Exon 23 of 24	NP_001264301.2	H7C5G6
	KIAA2012	NM_001367720.2		c.3430T>G	p.Phe1144Val	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>G	p.Phe1145Val	missense	Exon 23 of 24	ENSP00000419834.2	H7C5G6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 247112 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 125276

African (AFR) AF: 0.00 AC: 0 AN: 7184

American (AMR) AF: 0.00 AC: 0 AN: 7476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9236

East Asian (EAS) AF: 0.00 AC: 0 AN: 22894

South Asian (SAS) AF: 0.00 AC: 0 AN: 3036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158356

Other (OTH) AF: 0.00 AC: 0 AN: 16384

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.63
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.20	T
PhyloP100		1.6
GERP RS		3.9
gMVP		0.028

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;