2-148875582-A-C

Variant names:

• chr2-148875582-A-C
• rs762542110
• NM_004522.3:c.-36A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_004522.3(KIF5C):​c.-36A>C 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (0 hom., cov: 0)
  • Exomes 𝑓: 0.16 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF5C NM_004522.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0630
• 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-AS1 (HGNC:40325): (KIF5C antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 2-148875582-A-C is Benign according to our data. Variant chr2-148875582-A-C is described in ClinVar as Benign. ClinVar VariationId is 683963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.-36A>C		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.-36A>C		5_prime_UTR	Exon 1 of 26	ENSP00000393379.1	O60282-1
	KIF5C	ENST00000677891.1		c.-36A>C		5_prime_UTR	Exon 1 of 26	ENSP00000503013.1	O60282-1
	KIF5C	ENST00000677280.1		c.-36A>C		5_prime_UTR	Exon 1 of 26	ENSP00000503955.1	A0A7I2V492

Frequencies

GnomAD3 genomes AF: 0.00696 AC: 357 AN: 51320 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00599

Gnomad AMI AF: 0.00385

Gnomad AMR AF: 0.00564

Gnomad ASJ AF: 0.00820

Gnomad EAS AF: 0.00272

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.00888

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00818

Gnomad OTH AF: 0.00448

GnomAD2 exomes AF: 0.155 AC: 9541 AN: 61730 AF XY: 0.144

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.317

Gnomad FIN exome AF: 0.0494

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.187

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.161 AC: 31237 AN: 193664 Hom.: 3 Cov.: 4 AF XY: 0.156 AC XY: 16076 AN XY: 103322

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

African (AFR) AF: 0.216 AC: 1138 AN: 5276

American (AMR) AF: 0.314 AC: 3849 AN: 12258

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 1061 AN: 7494

East Asian (EAS) AF: 0.127 AC: 1216 AN: 9556

South Asian (SAS) AF: 0.168 AC: 3360 AN: 20052

European-Finnish (FIN) AF: 0.0784 AC: 1241 AN: 15834

Middle Eastern (MID) AF: 0.155 AC: 126 AN: 812

European-Non Finnish (NFE) AF: 0.157 AC: 17707 AN: 112460

Other (OTH) AF: 0.155 AC: 1539 AN: 9922

⚠️ 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: 0.00697 AC: 358 AN: 51342 Hom.: 0 Cov.: 0 AF XY: 0.00668 AC XY: 167 AN XY: 25012

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

African (AFR) AF: 0.00605 AC: 82 AN: 13562

American (AMR) AF: 0.00564 AC: 29 AN: 5138

Ashkenazi Jewish (ASJ) AF: 0.00820 AC: 10 AN: 1220

East Asian (EAS) AF: 0.00272 AC: 6 AN: 2202

South Asian (SAS) AF: 0.00458 AC: 7 AN: 1528

European-Finnish (FIN) AF: 0.00888 AC: 26 AN: 2928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 114

European-Non Finnish (NFE) AF: 0.00818 AC: 194 AN: 23714

Other (OTH) AF: 0.00444 AC: 3 AN: 676

⚠️ 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.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		-0.063
PromoterAI		0.25	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: rs762542110; hg19: chr2-149633151;