rs10113275

Variant names:

• chr8-38903665-C-G
• rs10113275
• NM_021623.2:c.-24+2220C>G

Variant summary

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

The ENST00000617275.5(PLEKHA2):​c.-24+2220C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,130 control chromosomes in the GnomAD database, including 3,470 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 0.21 (3470 hom., cov: 32)
• Consequence: PLEKHA2 ENST00000617275.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 3 publications found

Genes affected

PLEKHA2 (HGNC:14336): (pleckstrin homology domain containing A2) Enables fibronectin binding activity; laminin binding activity; and phosphatidylinositol-3,4-bisphosphate binding activity. Involved in positive regulation of cell-matrix adhesion. Located in cytoplasm and membrane. Part of protein-containing complex. [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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000617275.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA2	NM_021623.2	MANE Select	c.-24+2220C>G		intron	N/A	NP_067636.1
	PLEKHA2	NM_001410925.1		c.-10+1773C>G		intron	N/A	NP_001397854.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA2	ENST00000617275.5	TSL:2 MANE Select	c.-24+2220C>G		intron	N/A	ENSP00000482228.1
	PLEKHA2	ENST00000616834.1	TSL:5	c.-24+1596C>G		intron	N/A	ENSP00000483078.1
	PLEKHA2	ENST00000616927.4	TSL:5	c.-10+2220C>G		intron	N/A	ENSP00000482319.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32047 AN: 152012 Hom.: 3465 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.211 AC: 32069 AN: 152130 Hom.: 3470 Cov.: 32 AF XY: 0.209 AC XY: 15575 AN XY: 74384

African (AFR) AF: 0.256 AC: 10639 AN: 41488

American (AMR) AF: 0.218 AC: 3328 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3470

East Asian (EAS) AF: 0.0125 AC: 65 AN: 5188

South Asian (SAS) AF: 0.133 AC: 643 AN: 4826

European-Finnish (FIN) AF: 0.209 AC: 2214 AN: 10574

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13782 AN: 67980

Other (OTH) AF: 0.195 AC: 411 AN: 2110

Alfa AF: 0.205 Hom.: 387

Bravo AF: 0.216

Asia WGS AF: 0.107 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.1
DANN	Benign	0.69
PhyloP100		-1.8
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: rs10113275; hg19: chr8-38761183;