3-111919285-A-T

Variant names:

• chr3-111919285-A-T
• rs951660
• NM_001134438.2:c.1863+70A>T

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 8 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: 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 (BayesDel_noAF=-0.83).

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.1863+70A>T		intron	N/A	NP_001127910.1	Q86SQ0-1
	PHLDB2	NM_001134439.2		c.1863+70A>T		intron	N/A	NP_001127911.1	Q86SQ0-1
	PHLDB2	NM_001134437.2		c.1944+70A>T		intron	N/A	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.1863+70A>T		intron	N/A	ENSP00000405405.2	Q86SQ0-1
	PHLDB2	ENST00000393925.7	TSL:1	c.1863+70A>T		intron	N/A	ENSP00000377502.3	Q86SQ0-1
	PHLDB2	ENST00000481953.5	TSL:1	c.1863+70A>T		intron	N/A	ENSP00000418319.1	Q86SQ0-2

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.26
PhyloP100		-0.56

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: rs951660; hg19: chr3-111638132;