8-144473998-GCTC-G

Position:

• chr8-144473998-GCTC-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001369769.2(KIFC2):​c.*612_*614del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 568,502 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00075 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: KIFC2 NM_001369769.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.903

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]

FOXH1 (HGNC:3814): (forkhead box H1) FOXH1 encodes a human homolog of Xenopus forkhead activin signal transducer-1. FOXH1 protein binds SMAD2 and activates an activin response element via binding the DNA motif TGT(G/T)(T/G)ATT. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIFC2	NM_001369769.2	c.*612_*614del		3_prime_UTR_variant	18/18	ENST00000645548.2
FOXH1	NM_003923.3	c.*237_*239del		3_prime_UTR_variant	3/3	ENST00000377317.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXH1	ENST00000377317.5	c.*237_*239del		3_prime_UTR_variant	3/3	1	NM_003923.3	P1
KIFC2	ENST00000645548.2	c.*612_*614del		3_prime_UTR_variant	18/18		NM_001369769.2	P1
KIFC2	ENST00000301332.3	c.*551_*553del		3_prime_UTR_variant	17/17	1
KIFC2	ENST00000643461.1	n.3445_3447del		non_coding_transcript_exon_variant	17/17

Frequencies

GnomAD3 genomes AF: 0.000755 AC: 115 AN: 152220 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.00123 AC: 512 AN: 416164 Hom.: 2 AF XY: 0.00159 AC XY: 344 AN XY: 216762

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00343

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00655

Gnomad4 FIN exome AF: 0.0000354

Gnomad4 NFE exome AF: 0.000601

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.000748 AC: 114 AN: 152338 Hom.: 2 Cov.: 32 AF XY: 0.00102 AC XY: 76 AN XY: 74484

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000594 Hom.: 0

Bravo AF: 0.000703

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Holoprosencephaly sequence Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs550365735; hg19: chr8-145699381;