chr11-66265209-C-T

Variant names:

• chr11-66265209-C-T
• rs147513948
• NM_001318734.2:c.1308C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001318734.2(KLC2):​c.1308C>T​(p.Ser436Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.00375 in 1,514,820 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (19 hom.)
• Consequence: KLC2 NM_001318734.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.12
• Publications: 2 publications found

Genes affected

KLC2 (HGNC:20716): (kinesin light chain 2) The protein encoded by this gene is a light chain of kinesin, a molecular motor responsible for moving vesicles and organelles along microtubules. Defects in this gene are a cause of spastic paraplegia, optic atrophy, and neuropathy (SPOAN) syndrome. [provided by RefSeq, Mar 2016]

KLC2-AS1 (HGNC:40934): (KLC2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 11-66265209-C-T is Benign according to our data. Variant chr11-66265209-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 774626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 19 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318734.2. 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
	KLC2	NM_001318734.2	MANE Select	c.1308C>T	p.Ser436Ser	synonymous	Exon 11 of 16	NP_001305663.1	Q9H0B6-1
	KLC2	NM_001134775.2		c.1308C>T	p.Ser436Ser	synonymous	Exon 11 of 16	NP_001128247.1	Q9H0B6-1
	KLC2	NM_001134776.2		c.1308C>T	p.Ser436Ser	synonymous	Exon 11 of 16	NP_001128248.1	Q9H0B6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLC2	ENST00000394067.7	TSL:1 MANE Select	c.1308C>T	p.Ser436Ser	synonymous	Exon 11 of 16	ENSP00000377631.2	Q9H0B6-1
	KLC2	ENST00000316924.9	TSL:1	c.1308C>T	p.Ser436Ser	synonymous	Exon 11 of 16	ENSP00000314837.5	Q9H0B6-1
	KLC2	ENST00000917341.1		c.1308C>T	p.Ser436Ser	synonymous	Exon 11 of 16	ENSP00000587400.1

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 386 AN: 149932 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000632

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000928

Gnomad ASJ AF: 0.00204

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00171

Gnomad FIN AF: 0.00560

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00404

Gnomad OTH AF: 0.00145

GnomAD2 exomes AF: 0.00283 AC: 710 AN: 250974 AF XY: 0.00301

Gnomad AFR exome AF: 0.000872

Gnomad AMR exome AF: 0.000608

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00545

Gnomad NFE exome AF: 0.00379

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00388 AC: 5289 AN: 1364754 Hom.: 19 Cov.: 34 AF XY: 0.00384 AC XY: 2609 AN XY: 678970

African (AFR) AF: 0.000512 AC: 16 AN: 31236

American (AMR) AF: 0.000590 AC: 25 AN: 42340

Ashkenazi Jewish (ASJ) AF: 0.00204 AC: 47 AN: 23022

East Asian (EAS) AF: 0.00 AC: 0 AN: 33822

South Asian (SAS) AF: 0.00301 AC: 257 AN: 85306

European-Finnish (FIN) AF: 0.00588 AC: 258 AN: 43858

Middle Eastern (MID) AF: 0.00816 AC: 43 AN: 5270

European-Non Finnish (NFE) AF: 0.00428 AC: 4473 AN: 1045450

Other (OTH) AF: 0.00312 AC: 170 AN: 54450

GnomAD4 genome AF: 0.00257 AC: 386 AN: 150066 Hom.: 1 Cov.: 33 AF XY: 0.00266 AC XY: 195 AN XY: 73318

African (AFR) AF: 0.000630 AC: 26 AN: 41260

American (AMR) AF: 0.000927 AC: 14 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.00204 AC: 7 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 5012

South Asian (SAS) AF: 0.00171 AC: 8 AN: 4666

European-Finnish (FIN) AF: 0.00560 AC: 56 AN: 10006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00404 AC: 272 AN: 67316

Other (OTH) AF: 0.00143 AC: 3 AN: 2092

Alfa AF: 0.00288 Hom.: 0

Bravo AF: 0.00199

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00354

EpiControl AF: 0.00403

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.94
PhyloP100		4.1
Mutation Taster		=83/17	polymorphism

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: rs147513948; hg19: chr11-66032680;