NM_001134438.2:c.1863+70A>T

Variant names:

• chr3-111919285-A-T
• rs951660
• NM_001134438.2:c.1863+70A>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.1863+70A>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHLDB2 NM_001134438.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556

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 (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDB2	NM_001134438.2	c.1863+70A>T		intron_variant	Intron 4 of 17	ENST00000431670.7	NP_001127910.1
PHLDB2	NM_001134439.2	c.1863+70A>T		intron_variant	Intron 4 of 17		NP_001127911.1
PHLDB2	NM_001134437.2	c.1944+70A>T		intron_variant	Intron 5 of 17		NP_001127909.1
PHLDB2	NM_145753.2	c.1863+70A>T		intron_variant	Intron 4 of 16		NP_665696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDB2	ENST00000431670.7	c.1863+70A>T		intron_variant	Intron 4 of 17	1	NM_001134438.2	ENSP00000405405.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.26

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

LitVar

Other links and lift over

dbSNP: rs951660; hg19: chr3-111638132;