DNMBP p.Ser1440Ser

Variant names:

• chr10-99880038-T-T
• NM_015221.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr10-99880039--
• chr10-99880039-G-A
• chr10-99880039-G-T
• chr10-99880039-G-C
• chr10-99880040-GA-CT
• chr10-99880039-GGA-ACT

Variant summary

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

The NM_015221.4(DNMBP):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNMBP NM_015221.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.845
• Publications: 0 publications found

Genes affected

DNMBP (HGNC:30373): (dynamin binding protein) This gene encodes a protein belonging to the guanine nucleotide exchange factor family, and which regulates the configuration of cell junctions. It contains multiple binding sites for dynamin and thus links dynamin to actin regulatory proteins. Polymorphisms in this gene have been linked to Alzheimer's disease in some populations, though there are conflicting reports of such linkages in other populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

DNMBP Gene-Disease associations (from GenCC):

• cataract 48

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015221.4. 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
	DNMBP	NM_015221.4	MANE Select	c.		exon_region	Exon 16 of 17	NP_056036.1	Q6XZF7-1
	DNMBP	NM_001441287.1		c.		exon_region	Exon 17 of 18	NP_001428216.1
	DNMBP	NM_001441288.1		c.		exon_region	Exon 15 of 16	NP_001428217.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMBP	ENST00000324109.9	TSL:1 MANE Select	c.		exon_region	Exon 16 of 17	ENSP00000315659.4	Q6XZF7-1
	DNMBP	ENST00000543621.6	TSL:1	c.		exon_region	Exon 13 of 14	ENSP00000443657.2	A0A1C7CYY6
	DNMBP	ENST00000856964.1		c.		exon_region	Exon 17 of 18	ENSP00000527023.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.84

Splicing

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: chr10-101639795;