2-149005165-G-A

Variant names:

• chr2-149005165-G-A
• rs6435220
• NM_004522.3:c.2374-228G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004522.3(KIF5C):​c.2374-228G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,016 control chromosomes in the GnomAD database, including 36,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (36173 hom., cov: 31)
• Consequence: KIF5C NM_004522.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.992
• Publications: 1 publications found

Genes affected

KIF5C (HGNC:6325): (kinesin family member 5C) The protein encoded by this gene is a kinesin heavy chain subunit involved in the transport of cargo within the central nervous system. The encoded protein, which acts as a tetramer by associating with another heavy chain and two light chains, interacts with protein kinase CK2. Mutations in this gene have been associated with complex cortical dysplasia with other brain malformations-2. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Jul 2015]

KIF5C Gene-Disease associations (from GenCC):

• complex cortical dysplasia with other brain malformations 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 2-149005165-G-A is Benign according to our data. Variant chr2-149005165-G-A is described in ClinVar as Benign. ClinVar VariationId is 1252331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004522.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5C	NM_004522.3	MANE Select	c.2374-228G>A		intron	N/A	NP_004513.1
	KIF5C	NR_111932.2		n.1746-228G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5C	ENST00000435030.6	TSL:1 MANE Select	c.2374-228G>A		intron	N/A	ENSP00000393379.1
	KIF5C	ENST00000464066.6	TSL:1	n.2239-228G>A		intron	N/A
	KIF5C	ENST00000482151.1	TSL:1	n.652-228G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103753 AN: 151898 Hom.: 36119 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.689

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.683 AC: 103864 AN: 152016 Hom.: 36173 Cov.: 31 AF XY: 0.680 AC XY: 50497 AN XY: 74298

African (AFR) AF: 0.796 AC: 32995 AN: 41456

American (AMR) AF: 0.669 AC: 10217 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2501 AN: 3472

East Asian (EAS) AF: 0.303 AC: 1566 AN: 5168

South Asian (SAS) AF: 0.667 AC: 3206 AN: 4808

European-Finnish (FIN) AF: 0.646 AC: 6822 AN: 10556

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44355 AN: 67964

Other (OTH) AF: 0.685 AC: 1445 AN: 2110

Alfa AF: 0.666 Hom.: 19688

Bravo AF: 0.686

Asia WGS AF: 0.541 AC: 1880 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.061
DANN	Benign	0.45
PhyloP100		-0.99

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: rs6435220; hg19: chr2-149861679;