10-99955231-T-C

Variant names:

• chr10-99955231-T-C
• rs550679455
• NM_015221.4:c.2243A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015221.4(DNMBP):​c.2243A>G​(p.Glu748Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: DNMBP NM_015221.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.66
• 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-AS1 (HGNC:20431): (DNMBP antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07719779).

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.2243A>G	p.Glu748Gly	missense	Exon 4 of 17	NP_056036.1	Q6XZF7-1
	DNMBP	NM_001441287.1		c.2243A>G	p.Glu748Gly	missense	Exon 5 of 18	NP_001428216.1
	DNMBP	NM_001441288.1		c.2243A>G	p.Glu748Gly	missense	Exon 4 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.2243A>G	p.Glu748Gly	missense	Exon 4 of 17	ENSP00000315659.4	Q6XZF7-1
	DNMBP	ENST00000856964.1		c.2243A>G	p.Glu748Gly	missense	Exon 5 of 18	ENSP00000527023.1
	DNMBP	ENST00000928782.1		c.2243A>G	p.Glu748Gly	missense	Exon 6 of 19	ENSP00000598841.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250516 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461116 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6 AN XY: 726746

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.000224 AC: 10 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111428

Other (OTH) AF: 0.000116 AC: 7 AN: 60358

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74446

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.00131 AC: 20 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000419

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.097
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.040	B
Vest4		0.17
MutPred		0.25		Loss of solvent accessibility (P = 0.0187)
MVP		0.61
MPC		0.22
ClinPred		0.87	D
GERP RS		5.8
Varity_R		0.18
gMVP		0.41
Mutation Taster		=61/39	polymorphism

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: rs550679455; hg19: chr10-101714988;