rs183760043

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015221.4(DNMBP):​c.2108G>C​(p.Arg703Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R703Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

DNMBP
NM_015221.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0380
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-AS1 (HGNC:20431): (DNMBP antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058407426).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNMBPNM_015221.4 linkc.2108G>C p.Arg703Pro missense_variant Exon 4 of 17 ENST00000324109.9 NP_056036.1 Q6XZF7-1
DNMBPXM_011539559.3 linkc.2108G>C p.Arg703Pro missense_variant Exon 5 of 18 XP_011537861.1 Q6XZF7-1
DNMBPXM_047424910.1 linkc.2108G>C p.Arg703Pro missense_variant Exon 5 of 18 XP_047280866.1
DNMBP-AS1NR_024130.3 linkn.177-308C>G intron_variant Intron 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNMBPENST00000324109.9 linkc.2108G>C p.Arg703Pro missense_variant Exon 4 of 17 1 NM_015221.4 ENSP00000315659.4 Q6XZF7-1
DNMBP-AS1ENST00000434409.2 linkn.173-308C>G intron_variant Intron 2 of 4 2
DNMBP-AS1ENST00000661150.1 linkn.177-1423C>G intron_variant Intron 2 of 2
DNMBP-AS1ENST00000661385.1 linkn.223-1116C>G intron_variant Intron 2 of 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251442
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.057
T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.058
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.020
Sift
Benign
0.049
D
Sift4G
Uncertain
0.025
D
Polyphen
0.39
B
Vest4
0.18
MutPred
0.24
Loss of stability (P = 0.0325);
MVP
0.50
MPC
0.27
ClinPred
0.23
T
GERP RS
2.2
Varity_R
0.36
gMVP
0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs183760043; hg19: chr10-101715123; API