2-202196996-G-C

Variant names:

• chr2-202196996-G-C
• rs1436596373
• NM_001277372.4:c.3384G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001277372.4(KIAA2012):​c.3384G>C​(p.Thr1128Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T1128T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KIAA2012 NM_001277372.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 0 publications found

Genes affected

KIAA2012 (HGNC:51250): (KIAA2012)

ENSG00000231903 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=1.41 with no splicing effect.

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.3384G>C	p.Thr1128Thr	synonymous	Exon 22 of 24	NP_001264301.2	H7C5G6
	KIAA2012	NM_001367720.2		c.3381G>C	p.Thr1127Thr	synonymous	Exon 22 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.3384G>C	p.Thr1128Thr	synonymous	Exon 22 of 24	ENSP00000419834.2	H7C5G6
	KIAA2012	ENST00000469462.1	TSL:1	n.4269G>C		non_coding_transcript_exon	Exon 10 of 10
	ENSG00000231903	ENST00000447111.2	TSL:2	n.98+4878C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398348 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689688

African (AFR) AF: 0.0000316 AC: 1 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078980

Other (OTH) AF: 0.00 AC: 0 AN: 57994

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.55
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

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: rs1436596373; hg19: chr2-203061719;