Genetic Variant NM_001198784.2:c.19-72G>A (chr15-55418151-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001198784.2(PIERCE2):c.19-72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 1,570,092 control chromosomes in the GnomAD database, including 227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 99 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 128 hom. )

Consequence

PIERCE2
NM_001198784.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00200

Variant links:

Genes affected

PIERCE2 (HGNC:44654): (piercer of microtubule wall 2)

PIERCE2 links:

DNAAF4 (HGNC:21493): (dynein axonemal assembly factor 4) This gene encodes a tetratricopeptide repeat domain-containing protein. The encoded protein interacts with estrogen receptors and the heat shock proteins, Hsp70 and Hsp90. An homologous protein in rat has been shown to function in neuronal migration in the developing neocortex. A chromosomal translocation involving this gene is associated with a susceptibility to developmental dyslexia. Mutations in this gene are associated with deficits in reading and spelling. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream cell cycle progression 1 (CCPG1) gene. [provided by RefSeq, Mar 2011]

DNAAF4 links:

DNAAF4-CCPG1 (HGNC:43019): (DNAAF4-CCPG1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring dyslexia susceptibility 1 candidate 1 (DYX1C1) and cell cycle progression 1 (CCPG1) genes on chromosome 15. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

DNAAF4-CCPG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 15-55418151-G-A is Benign according to our data. Variant chr15-55418151-G-A is described in ClinVar as [Benign]. Clinvar id is 3767094.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PIERCE2	NM_001198784.2 link	c.19-72G>A	intron_variant	Intron 1 of 1	ENST00000569691.2	NP_001185713.1	H3BRN8
DNAAF4	NM_001033560.2 link	c.1048-18C>T	intron_variant	Intron 8 of 8		NP_001028732.1	Q8WXU2-2A0A0S2Z5Z4
DNAAF4-CCPG1	NR_037923.1 link	n.1408+14346C>T	intron_variant	Intron 8 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIERCE2	ENST00000569691.2 link	c.19-72G>A		intron_variant	Intron 1 of 1	1	NM_001198784.2	ENSP00000456337.1		H3BRN8

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3190

AN:

152190

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0698

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00733

AC:

1511

AN:

206104

Hom.:

AF XY:

0.00572

AC XY:

635

AN XY:

110998

show subpopulations

Gnomad AFR exome

AF:

0.0745

Gnomad AMR exome

AF:

0.00684

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000347

Gnomad FIN exome

AF:

0.000709

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00557

GnomAD4 exome

AF:

0.00295

AC:

4188

AN:

1417784

Hom.:

128

Cov.:

AF XY:

0.00276

AC XY:

1945

AN XY:

703486

show subpopulations

Gnomad4 AFR exome

AF:

0.0740

Gnomad4 AMR exome

AF:

0.00729

Gnomad4 ASJ exome

AF:

0.00140

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.000672

Gnomad4 NFE exome

AF:

0.000986

Gnomad4 OTH exome

AF:

0.00664

GnomAD4 genome

AF:

0.0210

AC:

3192

AN:

152308

Hom.:

Cov.:

AF XY:

0.0201

AC XY:

1494

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0696

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.0243

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 10, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.38

DANN

Benign

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over