chr8-22578889-C-G

Variant names:

• chr8-22578889-C-G
• ENST00000308354.11:c.110C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021630.6(PDLIM2):​c.110C>G​(p.Pro37Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,085,890 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P37L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: PDLIM2 NM_021630.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.41
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06469837).

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.110C>G	p.Pro37Arg	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.110C>G	p.Pro37Arg	missense	Exon 1 of 10	ENSP00000312634.7	Q96JY6-5
	PDLIM2	ENST00000339162.11	TSL:1	c.110C>G	p.Pro37Arg	missense	Exon 1 of 10	ENSP00000342035.8	Q96JY6-5
	PDLIM2	ENST00000884623.1		c.-3+756C>G		intron	N/A	ENSP00000554682.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1085890 Hom.: 0 Cov.: 30 AF XY: 0.00000390 AC XY: 2 AN XY: 513120

African (AFR) AF: 0.00 AC: 0 AN: 23050

American (AMR) AF: 0.00 AC: 0 AN: 8434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14452

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 20260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4464

European-Non Finnish (NFE) AF: 0.00000217 AC: 2 AN: 923340

Other (OTH) AF: 0.00 AC: 0 AN: 44026

GnomAD4 genome Cov.: 33

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	0.080
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.11
DANN	Benign	0.44
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0064	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.031
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Vest4		0.084
MutPred		0.16		Gain of MoRF binding (P = 0.0057)
MVP		0.10
MPC		0.40
ClinPred		0.096	T
GERP RS		-7.3
PromoterAI		0.027	Neutral
gMVP		0.11
Mutation Taster		=94/6	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

hg19: chr8-22436402;