8-144474005-C-T

Variant names:

• chr8-144474005-C-T
• rs11781640
• NM_001369769.2:c.*616C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001369769.2(KIFC2):​c.*616C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00523 in 568,934 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (5 hom.)
• Consequence: KIFC2 NM_001369769.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.449
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 8-144474005-C-T is Benign according to our data. Variant chr8-144474005-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 909983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 gene

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.*616C>T		3_prime_UTR	Exon 18 of 18	NP_001356698.1	A0A2R8YEU8
	FOXH1	NM_003923.3	MANE Select	c.*233G>A		3_prime_UTR	Exon 3 of 3	NP_003914.1	O75593
	KIFC2	NM_145754.5		c.*555C>T		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.*616C>T		3_prime_UTR	Exon 18 of 18	ENSP00000494595.1	A0A2R8YEU8
	FOXH1	ENST00000377317.5	TSL:1 MANE Select	c.*233G>A		3_prime_UTR	Exon 3 of 3	ENSP00000366534.4	O75593
	KIFC2	ENST00000301332.3	TSL:1	c.*555C>T		3_prime_UTR	Exon 17 of 17	ENSP00000301332.2	Q96AC6-1

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 620 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00689

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00565 AC: 2354 AN: 416596 Hom.: 5 Cov.: 3 AF XY: 0.00539 AC XY: 1169 AN XY: 217068

African (AFR) AF: 0.000832 AC: 10 AN: 12026

American (AMR) AF: 0.00406 AC: 68 AN: 16756

Ashkenazi Jewish (ASJ) AF: 0.00877 AC: 115 AN: 13116

East Asian (EAS) AF: 0.00 AC: 0 AN: 29828

South Asian (SAS) AF: 0.0000543 AC: 2 AN: 36834

European-Finnish (FIN) AF: 0.00250 AC: 71 AN: 28420

Middle Eastern (MID) AF: 0.00107 AC: 2 AN: 1874

European-Non Finnish (NFE) AF: 0.00779 AC: 1971 AN: 253084

Other (OTH) AF: 0.00466 AC: 115 AN: 24658

GnomAD4 genome AF: 0.00406 AC: 619 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.00342 AC XY: 255 AN XY: 74490

African (AFR) AF: 0.00132 AC: 55 AN: 41574

American (AMR) AF: 0.00287 AC: 44 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00688 AC: 468 AN: 68032

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00653 Hom.: 5

Bravo AF: 0.00412

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Holoprosencephaly sequence (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.60
PhyloP100		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11781640; hg19: chr8-145699388;