rs945105918

Variant names:

• chr8-22578802-C-A
• rs945105918
• ENST00000308354.11:c.23C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-22578802-C-A
• chr8-22578802-C-G
• chr8-22578802-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021630.6(PDLIM2):​c.23C>A​(p.Pro8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000739 in 1,081,994 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: PDLIM2 NM_021630.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12146008).

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.23C>A	p.Pro8Gln	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.23C>A	p.Pro8Gln	missense	Exon 1 of 10	ENSP00000312634.7	Q96JY6-5
	PDLIM2	ENST00000339162.11	TSL:1	c.23C>A	p.Pro8Gln	missense	Exon 1 of 10	ENSP00000342035.8	Q96JY6-5
	PDLIM2	ENST00000884623.1		c.-3+669C>A		intron	N/A	ENSP00000554682.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000739 AC: 8 AN: 1081994 Hom.: 0 Cov.: 30 AF XY: 0.00000978 AC XY: 5 AN XY: 511060

African (AFR) AF: 0.000174 AC: 4 AN: 23026

American (AMR) AF: 0.00 AC: 0 AN: 8424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14384

East Asian (EAS) AF: 0.00 AC: 0 AN: 26528

South Asian (SAS) AF: 0.00 AC: 0 AN: 19610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4482

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 920572

Other (OTH) AF: 0.0000684 AC: 3 AN: 43856

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.3
DANN	Benign	0.93
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.45
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.023
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.21
MutPred		0.14		Gain of helix (P = 0.005)
MVP		0.32
MPC		0.070
ClinPred		0.087	T
GERP RS		-1.9
PromoterAI		0.022	Neutral
gMVP		0.10
Mutation Taster		=98/2	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: rs945105918; hg19: chr8-22436315;