8-22578894-A-T

Variant names:

• chr8-22578894-A-T
• rs1026881236
• ENST00000308354.11:c.115A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021630.6(PDLIM2):​c.115A>T​(p.Ser39Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 1,238,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: PDLIM2 NM_021630.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.23
• Publications: 0 publications found

Genes affected

PDLIM2 (HGNC:13992): (PDZ and LIM domain 2) This gene encodes a member of the ALP subfamily of PDZ-LIM domain proteins. The encoded protein suppresses anchorage-dependent growth and promotes cell migration and adhesion through interactions with the actin cytoskeleton via the PDZ domain. The encoded protein is also a putative tumor suppressor protein, and decreased expression of this gene is associated with several malignancies including breast cancer and adult T-cell leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.072468996).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021630.6. 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
	PDLIM2	NM_021630.6		c.115A>T	p.Ser39Cys	missense	Exon 1 of 10	NP_067643.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM2	ENST00000308354.11	TSL:1	c.115A>T	p.Ser39Cys	missense	Exon 1 of 10	ENSP00000312634.7	Q96JY6-5
	PDLIM2	ENST00000339162.11	TSL:1	c.115A>T	p.Ser39Cys	missense	Exon 1 of 10	ENSP00000342035.8	Q96JY6-5
	PDLIM2	ENST00000884623.1		c.-3+761A>T		intron	N/A	ENSP00000554682.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000276 AC: 30 AN: 1085812 Hom.: 0 Cov.: 30 AF XY: 0.0000292 AC XY: 15 AN XY: 513068

African (AFR) AF: 0.000651 AC: 15 AN: 23044

American (AMR) AF: 0.000119 AC: 1 AN: 8432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14450

East Asian (EAS) AF: 0.00 AC: 0 AN: 26550

South Asian (SAS) AF: 0.00 AC: 0 AN: 20256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4462

European-Non Finnish (NFE) AF: 0.0000130 AC: 12 AN: 923274

Other (OTH) AF: 0.0000454 AC: 2 AN: 44022

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7 AN XY: 74352

African (AFR) AF: 0.000410 AC: 17 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.4
DANN	Benign	0.40
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.97	T
PhyloP100		-1.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.029
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.036	D
Vest4		0.16
MutPred		0.23		Loss of phosphorylation at S39 (P = 0.0259)
MVP		0.14
MPC		0.082
ClinPred		0.037	T
GERP RS		-5.1
PromoterAI		-0.023	Neutral
gMVP		0.083
Mutation Taster		=97/3	polymorphism

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: rs1026881236; hg19: chr8-22436407;