12-50640769-C-T

Position:

• chr12-50640769-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_173602.3(DIP2B):​c.218C>T​(p.Ala73Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DIP2B NM_173602.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.968

Genes affected

DIP2B (HGNC:29284): (disco interacting protein 2 homolog B) This gene encodes a member of the disco-interacting protein homolog 2 protein family. The encoded protein contains a binding site for the transcriptional regulator DNA methyltransferase 1 associated protein 1 as well as AMP-binding sites. The presence of these sites suggests that the encoded protein may participate in DNA methylation. This gene is located near a folate-sensitive fragile site, and CGG-repeat expansion in the promoter of this gene which affects transcription has been detected in individuals containing this fragile site on chromosome 12. [provided by RefSeq, Aug 2011]

DIP2B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DIP2B. . Gene score misZ 3.1809 (greater than the threshold 3.09). Trascript score misZ 4.0584 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, FRA12A type.
• BP4: Computational evidence support a benign effect (MetaRNN=0.12103784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIP2B	NM_173602.3	c.218C>T	p.Ala73Val	missense_variant	3/38	ENST00000301180.10	NP_775873.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIP2B	ENST00000301180.10	c.218C>T	p.Ala73Val	missense_variant	3/38	5	NM_173602.3	ENSP00000301180.5
DIP2B	ENST00000549620.5	n.374C>T		non_coding_transcript_exon_variant	3/8	1
DIP2B	ENST00000546719.1	n.-36C>T		upstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.218C>T (p.A73V) alteration is located in exon 3 (coding exon 3) of the DIP2B gene. This alteration results from a C to T substitution at nucleotide position 218, causing the alanine (A) at amino acid position 73 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.035
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.054
Sift	Benign	0.29	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.36		Loss of relative solvent accessibility (P = 0.0404);
MVP		0.068
MPC		0.35
ClinPred		0.43	T
GERP RS		5.7
Varity_R		0.066
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-51034552;