Variant 18-2587844-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_006101.3(NDC80):c.684C>T(p.Tyr228=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00889 in 1,612,872 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 97 hom. )

Consequence

NDC80
NM_006101.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.386

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 18-2587844-C-T is Benign according to our data. Variant chr18-2587844-C-T is described in ClinVar as [Benign]. Clinvar id is 773333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.386 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDC80	NM_006101.3 linkuse as main transcript	c.684C>T	p.Tyr228=	synonymous_variant	8/17	ENST00000261597.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDC80	ENST00000261597.9 linkuse as main transcript	c.684C>T	p.Tyr228=	synonymous_variant	8/17	1	NM_006101.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00610

AC:

928

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00541

AC:

1357

AN:

250986

Hom.:

AF XY:

0.00530

AC XY:

719

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00445

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00960

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.00918

AC:

13410

AN:

1460612

Hom.:

Cov.:

AF XY:

0.00881

AC XY:

6401

AN XY:

726656

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.00470

Gnomad4 ASJ exome

AF:

0.00218

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00157

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.00646

GnomAD4 genome

AF:

0.00609

AC:

928

AN:

152260

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00805

Hom.:

Bravo

AF:

0.00637

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00934

EpiControl

AF:

0.0103

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.7

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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