2-43737868-C-T

Variant names:

• chr2-43737868-C-T
• rs1368086
• NM_172069.4:c.2944-473C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172069.4(PLEKHH2):​c.2944-473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,096 control chromosomes in the GnomAD database, including 2,823 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 0.18 (2823 hom., cov: 32)
• Consequence: PLEKHH2 NM_172069.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172069.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHH2	NM_172069.4	MANE Select	c.2944-473C>T		intron	N/A	NP_742066.2	Q8IVE3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHH2	ENST00000282406.9	TSL:1 MANE Select	c.2944-473C>T		intron	N/A	ENSP00000282406.4	Q8IVE3-1
	PLEKHH2	ENST00000405000.6	TSL:1	n.4870-473C>T		intron	N/A
	PLEKHH2	ENST00000923731.1		c.2944-473C>T		intron	N/A	ENSP00000593790.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27644 AN: 151976 Hom.: 2819 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.182 AC: 27661 AN: 152096 Hom.: 2823 Cov.: 32 AF XY: 0.183 AC XY: 13619 AN XY: 74380

African (AFR) AF: 0.114 AC: 4724 AN: 41476

American (AMR) AF: 0.288 AC: 4404 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3472

East Asian (EAS) AF: 0.114 AC: 588 AN: 5174

South Asian (SAS) AF: 0.223 AC: 1075 AN: 4828

European-Finnish (FIN) AF: 0.211 AC: 2228 AN: 10562

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13218 AN: 67986

Other (OTH) AF: 0.197 AC: 416 AN: 2110

Alfa AF: 0.191 Hom.: 7589

Bravo AF: 0.186

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.36
DANN	Benign	0.32
PhyloP100		-0.96
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: rs1368086; hg19: chr2-43965007;