3-111884693-A-C

Variant names:

• chr3-111884693-A-C
• NM_001134438.2:c.616A>C

Variant summary

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

The NM_001134438.2(PHLDB2):​c.616A>C​(p.Lys206Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. K206N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHLDB2 NM_001134438.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69
• Publications: 0 publications found

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

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=0.25710994).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134438.2. 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
	PHLDB2	NM_001134438.2	MANE Select	c.616A>C	p.Lys206Gln	missense	Exon 2 of 18	NP_001127910.1	Q86SQ0-1
	PHLDB2	NM_001134439.2		c.616A>C	p.Lys206Gln	missense	Exon 2 of 18	NP_001127911.1	Q86SQ0-1
	PHLDB2	NM_001134437.2		c.697A>C	p.Lys233Gln	missense	Exon 3 of 18	NP_001127909.1	Q86SQ0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHLDB2	ENST00000431670.7	TSL:1 MANE Select	c.616A>C	p.Lys206Gln	missense	Exon 2 of 18	ENSP00000405405.2	Q86SQ0-1
	PHLDB2	ENST00000393925.7	TSL:1	c.616A>C	p.Lys206Gln	missense	Exon 2 of 18	ENSP00000377502.3	Q86SQ0-1
	PHLDB2	ENST00000481953.5	TSL:1	c.616A>C	p.Lys206Gln	missense	Exon 1 of 16	ENSP00000418319.1	Q86SQ0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	Uncertain	0.38
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.7
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.096
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.087	T
Polyphen		0.42	B
Vest4		0.42
MutPred		0.32		Loss of methylation at K206 (P = 0.0058)
MVP		0.64
MPC		0.18
ClinPred		0.93	D
GERP RS		5.6
PromoterAI		-0.013	Neutral
Varity_R		0.36
gMVP		0.23
Mutation Taster		=87/13	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: chr3-111603540;