rs142310829

Variant names:

• chr8-144466443-C-A
• rs142310829
• NM_001369769.2:c.24C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-144466443-C-A
• chr8-144466443-C-G
• chr8-144466443-C-T

Variant summary

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

The NM_001369769.2(KIFC2):​c.24C>A​(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000824 in 1,213,324 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. L8L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: KIFC2 NM_001369769.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 0 publications found

Genes affected

KIFC2 (HGNC:29530): (kinesin family member C2) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement and mitotic spindle assembly. Predicted to be located in cytoplasm. Predicted to be part of kinesin complex. Predicted to be active in microtubule cytoskeleton and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM276 (HGNC:56235): (transmembrane protein 276)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369769.2. 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
	KIFC2	NM_001369769.2	MANE Select	c.24C>A	p.Leu8Leu	synonymous	Exon 1 of 18	NP_001356698.1	A0A2R8YEU8
	KIFC2	NM_145754.5		c.24C>A	p.Leu8Leu	synonymous	Exon 1 of 17	NP_665697.1	Q96AC6-1
	TMEM276	NM_001408061.1		c.-355G>T		5_prime_UTR	Exon 1 of 3	NP_001394990.1	P0DTL5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFC2	ENST00000645548.2	MANE Select	c.24C>A	p.Leu8Leu	synonymous	Exon 1 of 18	ENSP00000494595.1	A0A2R8YEU8
	KIFC2	ENST00000301332.3	TSL:1	c.24C>A	p.Leu8Leu	synonymous	Exon 1 of 17	ENSP00000301332.2	Q96AC6-1
	KIFC2	ENST00000880943.1		c.24C>A	p.Leu8Leu	synonymous	Exon 1 of 19	ENSP00000551002.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 8.24e-7 AC: 1 AN: 1213324 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 600704

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24214

American (AMR) AF: 0.00 AC: 0 AN: 23350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18192

East Asian (EAS) AF: 0.00 AC: 0 AN: 24394

South Asian (SAS) AF: 0.00 AC: 0 AN: 56568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4682

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 977732

Other (OTH) AF: 0.00 AC: 0 AN: 46228

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		-0.082
PromoterAI		0.013	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 18

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

Other links and lift over

dbSNP: rs142310829; hg19: chr8-145691826;