XR_001739733.2:n.8269C>T

Variant names:

• chr2-148875049-G-A
• rs28363955
• XR_001739733.2:n.8269C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The XR_001739733.2(KIF5C-AS1):​n.8269C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0089 in 152,244 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0089 (21 hom., cov: 32)
• Consequence: KIF5C-AS1 XR_001739733.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.306
• Publications: 0 publications found

Genes affected

KIF5C-AS1 (HGNC:40325): (KIF5C antisense RNA 1)

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: Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-148875049-G-A is Benign according to our data. Variant chr2-148875049-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 672641.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0089 (1355/152244) while in subpopulation AFR AF = 0.0311 (1294/41562). AF 95% confidence interval is 0.0297. There are 21 homozygotes in GnomAd4. There are 630 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435030.6. 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
	KIF5C	NM_004522.3	MANE Select	c.-569G>A		upstream_gene	N/A	NP_004513.1	O60282-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5C-AS1	ENST00000601658.5	TSL:5	n.676+2177C>T		intron	N/A
	KIF5C	ENST00000435030.6	TSL:1 MANE Select	c.-569G>A		upstream_gene	N/A	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000677891.1		c.-569G>A		upstream_gene	N/A	ENSP00000503013.1	O60282-1

Frequencies

GnomAD3 genomes AF: 0.00888 AC: 1351 AN: 152126 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00910

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

GnomAD4 genome AF: 0.00890 AC: 1355 AN: 152244 Hom.: 21 Cov.: 32 AF XY: 0.00846 AC XY: 630 AN XY: 74426

African (AFR) AF: 0.0311 AC: 1294 AN: 41562

American (AMR) AF: 0.00229 AC: 35 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68014

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.00200 Hom.: 0

Bravo AF: 0.0102

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.89
PhyloP100		-0.31
PromoterAI		-0.11	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs28363955; hg19: chr2-149632618;