chr8-144466959-C-G

Variant names:

• chr8-144466959-C-G
• rs776124283
• NM_001369769.2:c.179C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001369769.2(KIFC2):​c.179C>G​(p.Ala60Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,591,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 36)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KIFC2 NM_001369769.2 missense, splice_region
• Scores: Splicing: ADA: 0.00005387
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05954075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC2	NM_001369769.2	c.179C>G	p.Ala60Gly	missense_variant, splice_region_variant	Exon 3 of 18	ENST00000645548.2	NP_001356698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFC2	ENST00000645548.2	c.179C>G	p.Ala60Gly	missense_variant, splice_region_variant	Exon 3 of 18		NM_001369769.2	ENSP00000494595.1
KIFC2	ENST00000301332.3	c.179C>G	p.Ala60Gly	missense_variant, splice_region_variant	Exon 3 of 17	1		ENSP00000301332.2
KIFC2	ENST00000642354.1	c.179C>G	p.Ala60Gly	missense_variant, splice_region_variant	Exon 3 of 18			ENSP00000496539.1
KIFC2	ENST00000643461.1	n.556C>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 17

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439764 Hom.: 0 Cov.: 72 AF XY: 0.00000140 AC XY: 1 AN XY: 716010

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 36 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.76
DEOGEN2	Benign	0.0019	.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.38	T;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	.;.;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.46	.;.;N
REVEL	Benign	0.098
Sift	Benign	1.0	.;.;T
Sift4G	Benign	1.0	.;.;T
Polyphen		0.0	.;.;B
Vest4		0.14
MutPred		0.043		Loss of stability (P = 0.0662);Loss of stability (P = 0.0662);Loss of stability (P = 0.0662);
MVP		0.33
ClinPred		0.048	T
GERP RS		0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000054
dbscSNV1_RF	Benign	0.066
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

Publications

LitVar

Other links and lift over

dbSNP: rs776124283; hg19: chr8-145692342;