18-2614476-A-T

Variant names:

• chr18-2614476-A-T
• rs182046301
• NM_006101.3:c.1792-1961A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006101.3(NDC80):​c.1792-1961A>T 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 0.0092 (3 hom., cov: 0)
  • Exomes 𝑓: 0.00088 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NDC80 NM_006101.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDC80	NM_006101.3	c.1792-1961A>T		intron_variant	Intron 16 of 16	ENST00000261597.9	NP_006092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDC80	ENST00000261597.9	c.1792-1961A>T		intron_variant	Intron 16 of 16	1	NM_006101.3	ENSP00000261597.4
NDC80	ENST00000574096.1	c.82-478A>T		intron_variant	Intron 1 of 1	3		ENSP00000458236.1

Frequencies

GnomAD3 genomes AF: 0.00924 AC: 29 AN: 3140 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.0172

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00690

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 216 AF XY: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000879 AC: 1 AN: 1138 Hom.: 0 Cov.: 0 AF XY: 0.00136 AC XY: 1 AN XY: 736

African (AFR) AF: 0.00 AC: 0 AN: 20

American (AMR) AF: 0.00 AC: 0 AN: 40

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 28

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 88

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 94

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.00123 AC: 1 AN: 812

Other (OTH) AF: 0.00 AC: 0 AN: 50

GnomAD4 genome AF: 0.00922 AC: 29 AN: 3144 Hom.: 3 Cov.: 0 AF XY: 0.00772 AC XY: 11 AN XY: 1424

African (AFR) AF: 0.0131 AC: 13 AN: 996

American (AMR) AF: 0.0189 AC: 4 AN: 212

Ashkenazi Jewish (ASJ) AF: 0.0172 AC: 1 AN: 58

East Asian (EAS) AF: 0.00 AC: 0 AN: 50

South Asian (SAS) AF: 0.00 AC: 0 AN: 42

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.00690 AC: 11 AN: 1594

Other (OTH) AF: 0.00 AC: 0 AN: 36

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.6
DANN	Benign	0.44
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs182046301; hg19: chr18-2614475;