18-2614476-A-G

Position:

• chr18-2614476-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006101.3(NDC80):​c.1792-1961A>G variant causes a intron change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (3 hom., cov: 0)
  • Exomes 𝑓: 0.044 (13 hom.)
  • Failed GnomAD Quality Control
• Consequence: NDC80 NM_006101.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned

Genes affected

NDC80 (HGNC:16909): (NDC80 kinetochore complex component) This gene encodes a component of the NDC80 kinetochore complex. The encoded protein consists of an N-terminal microtubule binding domain and a C-terminal coiled-coiled domain that interacts with other components of the complex. This protein functions to organize and stabilize microtubule-kinetochore interactions and is required for proper chromosome segregation. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0241 (73/3028) while in subpopulation SAS AF= 0.0476 (2/42). AF 95% confidence interval is 0.0234. There are 3 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDC80	NM_006101.3	c.1792-1961A>G		intron_variant		ENST00000261597.9	NP_006092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDC80	ENST00000261597.9	c.1792-1961A>G		intron_variant		1	NM_006101.3	ENSP00000261597.4
NDC80	ENST00000574096.1	c.82-478A>G		intron_variant		3		ENSP00000458236.1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 73 AN: 3024 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0476

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.0278

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0441 AC: 50 AN: 1134 Hom.: 13 Cov.: 0 AF XY: 0.0574 AC XY: 42 AN XY: 732

Gnomad4 AFR exome AF: 0.0500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0557

Gnomad4 OTH exome AF: 0.0800

GnomAD4 genome AF: 0.0241 AC: 73 AN: 3028 Hom.: 3 Cov.: 0 AF XY: 0.0226 AC XY: 31 AN XY: 1370

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0476

Gnomad4 FIN AF: 0.0154

Gnomad4 NFE AF: 0.0227

Gnomad4 OTH AF: 0.0278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.6
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs182046301; hg19: chr18-2614475;