2-133349976-G-C

Variant names:

• chr2-133349976-G-C
• rs1346776
• NM_207363.3:c.70-46866C>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.70-46866C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,058 control chromosomes in the GnomAD database, including 6,245 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 0.27 (6245 hom., cov: 32)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCKAP5	NM_207363.3	c.70-46866C>G		intron_variant	Intron 3 of 19	ENST00000409261.6	NP_997246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCKAP5	ENST00000409261.6	c.70-46866C>G		intron_variant	Intron 3 of 19	5	NM_207363.3	ENSP00000387128.1
NCKAP5	ENST00000427594.5	c.55-46866C>G		intron_variant	Intron 1 of 4	1		ENSP00000399070.1
NCKAP5	ENST00000409213.5	c.70-46866C>G		intron_variant	Intron 3 of 17	5		ENSP00000386952.1
NCKAP5	ENST00000358991.4	c.70-46866C>G		intron_variant	Intron 2 of 3	5		ENSP00000351882.4

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40239 AN: 151940 Hom.: 6218 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.265 AC: 40314 AN: 152058 Hom.: 6245 Cov.: 32 AF XY: 0.262 AC XY: 19491 AN XY: 74322

African (AFR) AF: 0.433 AC: 17955 AN: 41458

American (AMR) AF: 0.231 AC: 3526 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 747 AN: 3468

East Asian (EAS) AF: 0.121 AC: 626 AN: 5182

South Asian (SAS) AF: 0.170 AC: 819 AN: 4818

European-Finnish (FIN) AF: 0.171 AC: 1800 AN: 10556

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14050 AN: 67982

Other (OTH) AF: 0.246 AC: 520 AN: 2112

Alfa AF: 0.116 Hom.: 169

Bravo AF: 0.278

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.44
PhyloP100		-1.6
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: rs1346776; hg19: chr2-134107548;