2-133259481-T-C

Variant names:

• chr2-133259481-T-C
• rs10193871
• NM_207363.3:c.143+43556A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207363.3(NCKAP5):​c.143+43556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,242 control chromosomes in the GnomAD database, including 964 homozygotes. 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 0.11 (964 hom., cov: 32)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939
• Publications: 11 publications found

Genes affected

NCKAP5 (HGNC:29847): (NCK associated protein 5) Predicted to be involved in microtubule bundle formation and microtubule depolymerization. Predicted to be active in microtubule plus-end. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207363.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP5	NM_207363.3	MANE Select	c.143+43556A>G		intron	N/A	NP_997246.2	O14513-1
	NCKAP5	NM_207481.4		c.143+43556A>G		intron	N/A	NP_997364.3	O14513-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP5	ENST00000409261.6	TSL:5 MANE Select	c.143+43556A>G		intron	N/A	ENSP00000387128.1	O14513-1
	NCKAP5	ENST00000427594.5	TSL:1	c.128+43556A>G		intron	N/A	ENSP00000399070.1	H7C187
	NCKAP5	ENST00000409213.5	TSL:5	c.143+43556A>G		intron	N/A	ENSP00000386952.1	O14513-2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16039 AN: 152124 Hom.: 965 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0879

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 16044 AN: 152242 Hom.: 964 Cov.: 32 AF XY: 0.106 AC XY: 7854 AN XY: 74434

African (AFR) AF: 0.0520 AC: 2161 AN: 41536

American (AMR) AF: 0.127 AC: 1940 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3468

East Asian (EAS) AF: 0.178 AC: 920 AN: 5174

South Asian (SAS) AF: 0.154 AC: 745 AN: 4826

European-Finnish (FIN) AF: 0.0879 AC: 933 AN: 10610

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8582 AN: 68018

Other (OTH) AF: 0.122 AC: 258 AN: 2116

Alfa AF: 0.0736 Hom.: 112

Bravo AF: 0.107

Asia WGS AF: 0.168 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10193871; hg19: chr2-134017053;