chr18-2595630-T-A

Position:

• chr18-2595630-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.293

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 -10 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_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDC80	NM_006101.3	c.1221+9T>A		intron_variant		ENST00000261597.9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00550 AC: 837 AN: 152200 Hom.: 4 Cov.: 32

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.: 14 AF XY: 0.00700 AC XY: 945 AN XY: 135008

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.: 66 Cov.: 30 AF XY: 0.00734 AC XY: 5324 AN XY: 725774

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.: 4 Cov.: 32 AF XY: 0.00557 AC XY: 415 AN XY: 74494

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.: 2

Bravo AF: 0.00416

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
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

Other links and lift over

dbSNP: rs117426949; hg19: chr18-2595629;