NM_001198784.2:c.19-72G>A

Variant names:

• chr15-55418151-G-A
• rs73406983
• NM_001198784.2:c.19-72G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00200
• Publications: 0 publications found

Genes affected

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

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-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]

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIERCE2	NM_001198784.2	c.19-72G>A		intron_variant	Intron 1 of 1	ENST00000569691.2	NP_001185713.1
DNAAF4	NM_001033560.2	c.1048-18C>T		intron_variant	Intron 8 of 8		NP_001028732.1
DNAAF4-CCPG1	NR_037923.1	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	c.19-72G>A		intron_variant	Intron 1 of 1	1	NM_001198784.2	ENSP00000456337.1

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3190 AN: 152190 Hom.: 100 Cov.: 33

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

GnomAD2 exomes AF: 0.00733 AC: 1511 AN: 206104 AF XY: 0.00572

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 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.: 29 AF XY: 0.00276 AC XY: 1945 AN XY: 703486

African (AFR) AF: 0.0740 AC: 2304 AN: 31154

American (AMR) AF: 0.00729 AC: 247 AN: 33892

Ashkenazi Jewish (ASJ) AF: 0.00140 AC: 32 AN: 22824

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39550

South Asian (SAS) AF: 0.000313 AC: 24 AN: 76758

European-Finnish (FIN) AF: 0.000672 AC: 35 AN: 52116

Middle Eastern (MID) AF: 0.0136 AC: 75 AN: 5516

European-Non Finnish (NFE) AF: 0.000986 AC: 1082 AN: 1097532

Other (OTH) AF: 0.00664 AC: 388 AN: 58442

GnomAD4 genome AF: 0.0210 AC: 3192 AN: 152308 Hom.: 99 Cov.: 33 AF XY: 0.0201 AC XY: 1494 AN XY: 74484

African (AFR) AF: 0.0696 AC: 2893 AN: 41556

American (AMR) AF: 0.0108 AC: 165 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00122 AC: 83 AN: 68030

Other (OTH) AF: 0.0152 AC: 32 AN: 2110

Alfa AF: 0.0139 Hom.: 11

Bravo AF: 0.0243

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.38
DANN	Benign	0.33
PhyloP100		-0.0020
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: rs73406983; hg19: chr15-55710349;