Genetic Variant DNMBP:c.2261-21193G>A (chr10-99930339-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001318326.2(DNMBP):c.425G>A(p.Cys142Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 703,024 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 28 hom. )

Consequence

DNMBP
NM_001318326.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.35

Publications

0 publications found

Variant links:

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 links:

DNMBP-AS1 (HGNC:20431): (DNMBP antisense RNA 1)

DNMBP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003171742).

BP6

Variant 10-99930339-C-T is Benign according to our data. Variant chr10-99930339-C-T is described in ClinVar as Benign. ClinVar VariationId is 3040160.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00118 (180/152312) while in subpopulation EAS AF = 0.0315 (163/5176). AF 95% confidence interval is 0.0275. There are 3 homozygotes in GnomAd4. There are 98 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318326.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNMBP	NM_015221.4	MANE Select	c.2261-21193G>A		intron	N/A	NP_056036.1	Q6XZF7-1
DNMBP	NM_001318326.2		c.425G>A	p.Cys142Tyr	missense	Exon 1 of 14	NP_001305255.1	A0A1B0GTX1
DNMBP	NM_001441287.1		c.2261-21193G>A		intron	N/A	NP_001428216.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNMBP	ENST00000324109.9	TSL:1 MANE Select	c.2261-21193G>A		intron	N/A	ENSP00000315659.4	Q6XZF7-1
DNMBP	ENST00000636706.1	TSL:2	c.425G>A	p.Cys142Tyr	missense	Exon 1 of 14	ENSP00000489875.1	A0A1B0GTX1
DNMBP	ENST00000856964.1		c.2261-21193G>A		intron	N/A	ENSP00000527023.1

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

181

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0316

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00286

AC:

385

AN:

134508

AF XY:

0.00258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0355

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000379

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.00222

AC:

1225

AN:

550712

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

624

AN XY:

298142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15808

American (AMR)

AF:

0.00

AC:

AN:

34714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20030

East Asian (EAS)

AF:

0.0358

AC:

1148

AN:

32104

South Asian (SAS)

AF:

0.000542

AC:

AN:

62776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.0000284

AC:

AN:

316978

Other (OTH)

AF:

0.00111

AC:

AN:

30606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

179

268

358

447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00118

AC:

180

AN:

152312

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41568

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0315

AC:

163

AN:

5176

South Asian (SAS)

AF:

0.00207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68034

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000323

Hom.:

Bravo

AF:

0.00153

ExAC

AF:

0.000492

AC:

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

DNMBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.20

(source)

DANN

Benign

0.55

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0032

PhyloP100

-2.3

GERP RS

-11

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over