rs753762885

Variant names:

• chr3-111884729-G-A
• NM_001134438.2:c.652G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-111884729-G-A
• chr3-111884729-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134438.2(PHLDB2):​c.652G>A​(p.Ala218Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. A218S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHLDB2 NM_001134438.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

Genes affected

PHLDB2 (HGNC:29573): (pleckstrin homology like domain family B member 2) Enables cadherin binding activity. Involved in several processes, including negative regulation of focal adhesion assembly; regulation of cytoskeleton organization; and regulation of embryonic development. Located in several cellular components, including basal cortex; cell leading edge; and intermediate filament cytoskeleton. Colocalizes with focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.014269114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDB2	NM_001134438.2	c.652G>A	p.Ala218Thr	missense_variant	Exon 2 of 18	ENST00000431670.7	NP_001127910.1
PHLDB2	NM_001134439.2	c.652G>A	p.Ala218Thr	missense_variant	Exon 2 of 18		NP_001127911.1
PHLDB2	NM_001134437.2	c.733G>A	p.Ala245Thr	missense_variant	Exon 3 of 18		NP_001127909.1
PHLDB2	NM_145753.2	c.652G>A	p.Ala218Thr	missense_variant	Exon 2 of 17		NP_665696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDB2	ENST00000431670.7	c.652G>A	p.Ala218Thr	missense_variant	Exon 2 of 18	1	NM_001134438.2	ENSP00000405405.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.012
DANN	Benign	0.64
DEOGEN2	Benign	0.0065	.;.;T;T;.;T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.024	T;T;.;T;T;T;T;.
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.014	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	.;N;N;.;.;.;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.16	N;N;N;N;N;N;N;N
REVEL	Benign	0.032
Sift	Benign	1.0	T;T;T;T;T;T;T;T
Sift4G	Benign	0.82	T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;.;B;B;B;B
Vest4		0.14
MutPred		0.073		.;Gain of glycosylation at S216 (P = 0.0382);Gain of glycosylation at S216 (P = 0.0382);Gain of glycosylation at S216 (P = 0.0382);Gain of glycosylation at S216 (P = 0.0382);Gain of glycosylation at S216 (P = 0.0382);Gain of glycosylation at S216 (P = 0.0382);Gain of glycosylation at S216 (P = 0.0382);
MVP		0.19
MPC		0.088
ClinPred		0.069	T
GERP RS		0.34
Varity_R		0.026
gMVP		0.18

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-111603576;