chr2-148875587-T-A

Variant names:

• chr2-148875587-T-A
• rs1558866657
• NM_004522.3:c.-31T>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004522.3(KIF5C):​c.-31T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000098 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.269
• Publications: 0 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-AS1 (HGNC:40325): (KIF5C antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 2-148875587-T-A is Benign according to our data. Variant chr2-148875587-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1203882.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5C	NM_004522.3	MANE Select	c.-31T>A		5_prime_UTR	Exon 1 of 26	NP_004513.1	O60282-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5C	ENST00000435030.6	TSL:1 MANE Select	c.-31T>A		5_prime_UTR	Exon 1 of 26	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000677891.1		c.-31T>A		5_prime_UTR	Exon 1 of 26	ENSP00000503013.1	O60282-1
	KIF5C	ENST00000677280.1		c.-31T>A		5_prime_UTR	Exon 1 of 26	ENSP00000503955.1	A0A7I2V492

Frequencies

GnomAD3 genomes AF: 0.00000981 AC: 1 AN: 101976 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000317

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000359 AC: 30 AN: 83652 AF XY: 0.000273

Gnomad AFR exome AF: 0.000557

Gnomad AMR exome AF: 0.000712

Gnomad ASJ exome AF: 0.000824

Gnomad EAS exome AF: 0.000542

Gnomad FIN exome AF: 0.000153

Gnomad NFE exome AF: 0.000231

Gnomad OTH exome AF: 0.000506

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00353 AC: 926 AN: 262460 Hom.: 0 Cov.: 0 AF XY: 0.00310 AC XY: 439 AN XY: 141586

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00485 AC: 33 AN: 6810

American (AMR) AF: 0.00635 AC: 80 AN: 12600

Ashkenazi Jewish (ASJ) AF: 0.00378 AC: 34 AN: 8996

East Asian (EAS) AF: 0.00291 AC: 31 AN: 10652

South Asian (SAS) AF: 0.00128 AC: 44 AN: 34492

European-Finnish (FIN) AF: 0.000713 AC: 17 AN: 23844

Middle Eastern (MID) AF: 0.00398 AC: 4 AN: 1006

European-Non Finnish (NFE) AF: 0.00416 AC: 631 AN: 151584

Other (OTH) AF: 0.00417 AC: 52 AN: 12476

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000980 AC: 1 AN: 102030 Hom.: 0 Cov.: 30 AF XY: 0.0000204 AC XY: 1 AN XY: 48962

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27378

American (AMR) AF: 0.00 AC: 0 AN: 9898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3752

South Asian (SAS) AF: 0.000317 AC: 1 AN: 3154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 250

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 48394

Other (OTH) AF: 0.00 AC: 0 AN: 1442

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	-0.59
CADD	Benign	15
DANN	Benign	0.92
PhyloP100		0.27
PromoterAI		0.031	Neutral

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: rs1558866657; hg19: chr2-149633156;