2-148922389-A-T

Position:

• chr2-148922389-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004522.3(KIF5C):​c.217+162A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 152,212 control chromosomes in the GnomAD database, including 48,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.77 (48781 hom., cov: 33)
• Consequence: KIF5C NM_004522.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.240

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-148922389-A-T is Benign according to our data. Variant chr2-148922389-A-T is described in ClinVar as [Benign]. Clinvar id is 1260232.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF5C	NM_004522.3	c.217+162A>T		intron_variant		ENST00000435030.6	NP_004513.1
LOC101928553	XR_923450.4	n.571-771T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF5C	ENST00000435030.6	c.217+162A>T		intron_variant		1	NM_004522.3	ENSP00000393379	P4
	ENST00000650778.1	n.985+3881T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116893 AN: 152094 Hom.: 48769 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.768 AC: 116922 AN: 152212 Hom.: 48781 Cov.: 33 AF XY: 0.775 AC XY: 57702 AN XY: 74436

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.799

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.909

Gnomad4 OTH AF: 0.783

Alfa AF: 0.830 Hom.: 6869

Bravo AF: 0.742

Asia WGS AF: 0.889 AC: 3091 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.3
DANN	Benign	0.80

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: rs4346318; hg19: chr2-149679958;