21-46497082-G-C

Variant names:

• chr21-46497082-G-C
• NM_015151.4:c.378G>C
• DIP2A p.Ser126Ser

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_015151.4(DIP2A):​c.378G>C​(p.Ser126Ser) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. S126S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DIP2A NM_015151.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 0 publications found

Genes affected

DIP2A (HGNC:17217): (disco interacting protein 2 homolog A) The protein encoded by this gene may be involved in axon patterning in the central nervous system. This gene is not highly expressed. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

DIP2A Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-2.06 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015151.4. 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
	DIP2A	NM_015151.4	MANE Select	c.378G>C	p.Ser126Ser	synonymous	Exon 4 of 38	NP_055966.2
	DIP2A	NM_001410751.1		c.378G>C	p.Ser126Ser	synonymous	Exon 4 of 39	NP_001397680.1	A0A494C143
	DIP2A	NM_001353942.2		c.378G>C	p.Ser126Ser	synonymous	Exon 4 of 38	NP_001340871.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIP2A	ENST00000417564.3	TSL:1 MANE Select	c.378G>C	p.Ser126Ser	synonymous	Exon 4 of 38	ENSP00000392066.2	Q14689-1
	DIP2A	ENST00000457905.7	TSL:1	c.378G>C	p.Ser126Ser	synonymous	Exon 4 of 22	ENSP00000393434.3	Q14689-4
	DIP2A	ENST00000466639.5	TSL:1	c.378G>C	p.Ser126Ser	synonymous	Exon 4 of 20	ENSP00000430249.1	Q14689-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.026
DANN	Benign	0.49
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-47916995;