rs13403030

Positions:

• chr2-43694816-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172069.4(PLEKHH2):​c.420+302A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,024 control chromosomes in the GnomAD database, including 5,405 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 0.25 (5405 hom., cov: 32)
• Consequence: PLEKHH2 NM_172069.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

Genes affected

PLEKHH2 (HGNC:30506): (pleckstrin homology, MyTH4 and FERM domain containing H2) Predicted to enable actin binding activity. Predicted to be involved in negative regulation of actin filament depolymerization. Located in several cellular components, including cytosol; lamellipodium; and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHH2	NM_172069.4	c.420+302A>T		intron_variant		ENST00000282406.9	NP_742066.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHH2	ENST00000282406.9	c.420+302A>T		intron_variant		1	NM_172069.4	ENSP00000282406	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37873 AN: 151906 Hom.: 5404 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.249 AC: 37873 AN: 152024 Hom.: 5405 Cov.: 32 AF XY: 0.251 AC XY: 18660 AN XY: 74298

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.0490

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.254

Alfa AF: 0.279 Hom.: 795

Bravo AF: 0.228

Asia WGS AF: 0.141 AC: 489 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.67

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: rs13403030; hg19: chr2-43921955;