rs562738425

Variant names:

• chr8-144474164-C-A
• rs562738425
• NM_001369769.2:c.*775C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-144474164-C-A
• chr8-144474164-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001369769.2(KIFC2):​c.*775C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000954 in 1,047,756 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: KIFC2 NM_001369769.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• 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]

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]

FOXH1 Gene-Disease associations (from GenCC):

• congenital heart malformation

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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.*775C>A		3_prime_UTR	Exon 18 of 18	NP_001356698.1	A0A2R8YEU8
	FOXH1	NM_003923.3	MANE Select	c.*74G>T		3_prime_UTR	Exon 3 of 3	NP_003914.1	O75593
	KIFC2	NM_145754.5		c.*714C>A		3_prime_UTR	Exon 17 of 17	NP_665697.1	Q96AC6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFC2	ENST00000645548.2	MANE Select	c.*775C>A		3_prime_UTR	Exon 18 of 18	ENSP00000494595.1	A0A2R8YEU8
	FOXH1	ENST00000377317.5	TSL:1 MANE Select	c.*74G>T		3_prime_UTR	Exon 3 of 3	ENSP00000366534.4	O75593
	FOXH1	ENST00000935088.1		c.*74G>T		3_prime_UTR	Exon 3 of 3	ENSP00000605147.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.54e-7 AC: 1 AN: 1047756 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 519748

African (AFR) AF: 0.00 AC: 0 AN: 23796

American (AMR) AF: 0.00 AC: 0 AN: 20998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17462

East Asian (EAS) AF: 0.00 AC: 0 AN: 34774

South Asian (SAS) AF: 0.00 AC: 0 AN: 59806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3690

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 799686

Other (OTH) AF: 0.00 AC: 0 AN: 45488

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.51
PhyloP100		-0.016

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: rs562738425; hg19: chr8-145699547;