2-132781130-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_207363.3(NCKAP5):c.4971C>T(p.Gly1657=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 1,613,872 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (45 hom.)
• Consequence: NCKAP5 NM_207363.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.56

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 2-132781130-G-A is Benign according to our data. Variant chr2-132781130-G-A is described in ClinVar as [Benign]. Clinvar id is 770870.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.56 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCKAP5	NM_207363.3	c.4971C>T	p.Gly1657=	synonymous_variant	15/20	ENST00000409261.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCKAP5	ENST00000409261.6	c.4971C>T	p.Gly1657=	synonymous_variant	15/20	5	NM_207363.3	P1
	ENST00000651100.1	n.458-33471G>A		intron_variant, non_coding_transcript_variant
NCKAP5	ENST00000409213.5	c.1093-7236C>T		intron_variant		5
NCKAP5	ENST00000473859.1	n.184C>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.00514 AC: 782 AN: 152108 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00748

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00426 AC: 1061 AN: 249028 Hom.: 8 AF XY: 0.00403 AC XY: 545 AN XY: 135098

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00597

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000393

Gnomad FIN exome AF: 0.00771

Gnomad NFE exome AF: 0.00671

Gnomad OTH exome AF: 0.00529

GnomAD4 exome AF: 0.00660 AC: 9647 AN: 1461646 Hom.: 45 Cov.: 31 AF XY: 0.00640 AC XY: 4650 AN XY: 727094

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.00563

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.00730

Gnomad4 NFE exome AF: 0.00789

Gnomad4 OTH exome AF: 0.00409

GnomAD4 genome AF: 0.00513 AC: 781 AN: 152226 Hom.: 6 Cov.: 33 AF XY: 0.00507 AC XY: 377 AN XY: 74414

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00720

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00944

Gnomad4 NFE AF: 0.00748

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00661 Hom.: 5

Bravo AF: 0.00424

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00556

EpiControl AF: 0.00623

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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	4.2
Dann	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs61742426; hg19: chr2-133538703;