chr2-148875010-A-G

Variant names:

• chr2-148875010-A-G
• rs150844317
• XR_001739733.2:n.8308T>C

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.8308T>C 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 0.00909 in 152,162 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0091 (17 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: 0.132
• 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=-0.84).
• BP6: Variant 2-148875010-A-G is Benign according to our data. Variant chr2-148875010-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1185865.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00909 (1383/152162) while in subpopulation AFR AF = 0.031 (1288/41520). AF 95% confidence interval is 0.0296. There are 17 homozygotes in GnomAd4. There are 659 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 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.-608A>G		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+2216T>C		intron	N/A
	KIF5C	ENST00000435030.6	TSL:1 MANE Select	c.-608A>G		upstream_gene	N/A	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000677891.1		c.-608A>G		upstream_gene	N/A	ENSP00000503013.1	O60282-1

Frequencies

GnomAD3 genomes AF: 0.00908 AC: 1381 AN: 152044 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00574

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

GnomAD4 genome AF: 0.00909 AC: 1383 AN: 152162 Hom.: 17 Cov.: 32 AF XY: 0.00886 AC XY: 659 AN XY: 74384

African (AFR) AF: 0.0310 AC: 1288 AN: 41520

American (AMR) AF: 0.00432 AC: 66 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

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

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68014

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.0101 Hom.: 3

Bravo AF: 0.0104

Asia WGS AF: 0.00173 AC: 6 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	-0.84
CADD	Benign	6.1
DANN	Benign	0.57
PhyloP100		0.13
PromoterAI		0.088	Neutral

Splicing

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

Other links and lift over

dbSNP: rs150844317; hg19: chr2-149632579;