Variant chr18-2595630-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006101.3(NDC80):c.1221+9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00681 in 1,611,170 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 66 hom. )

Consequence

NDC80
NM_006101.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.293

Variant links:

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]

NDC80 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 18-2595630-T-A is Benign according to our data. Variant chr18-2595630-T-A is described in ClinVar as [Benign]. Clinvar id is 771921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDC80	NM_006101.3 linkuse as main transcript	c.1221+9T>A		intron_variant		ENST00000261597.9	NP_006092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDC80	ENST00000261597.9 linkuse as main transcript	c.1221+9T>A		intron_variant		1	NM_006101.3	ENSP00000261597	P1

Frequencies

GnomAD3 genomes

AF:

0.00550

AC:

837

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00788

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00648

AC:

1615

AN:

249420

Hom.:

AF XY:

0.00700

AC XY:

945

AN XY:

135008

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.00270

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0122

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00755

Gnomad OTH exome

AF:

0.00658

GnomAD4 exome

AF:

0.00695

AC:

10140

AN:

1458852

Hom.:

Cov.:

AF XY:

0.00734

AC XY:

5324

AN XY:

725774

show subpopulations

Gnomad4 AFR exome

AF:

0.000779

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.00150

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0124

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.00704

Gnomad4 OTH exome

AF:

0.00659

GnomAD4 genome

AF:

0.00549

AC:

836

AN:

152318

Hom.:

Cov.:

AF XY:

0.00557

AC XY:

415

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00457

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.0117

Gnomad4 NFE

AF:

0.00788

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00679

Hom.:

Bravo

AF:

0.00416

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over