NM_015221.4:c.2000G>T

Variant names:

• chr10-99955474-C-A
• rs375606736
• NM_015221.4:c.2000G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015221.4(DNMBP):​c.2000G>T​(p.Arg667Leu) variant causes a missense 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. 16/22 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. R667H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNMBP NM_015221.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0342004).

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.2000G>T	p.Arg667Leu	missense	Exon 4 of 17	NP_056036.1	Q6XZF7-1
	DNMBP	NM_001441287.1		c.2000G>T	p.Arg667Leu	missense	Exon 5 of 18	NP_001428216.1
	DNMBP	NM_001441288.1		c.2000G>T	p.Arg667Leu	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.2000G>T	p.Arg667Leu	missense	Exon 4 of 17	ENSP00000315659.4	Q6XZF7-1
	DNMBP	ENST00000856964.1		c.2000G>T	p.Arg667Leu	missense	Exon 5 of 18	ENSP00000527023.1
	DNMBP	ENST00000928782.1		c.2000G>T	p.Arg667Leu	missense	Exon 6 of 19	ENSP00000598841.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0010
DANN	Benign	0.69
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-2.1
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.029
Sift	Benign	0.53	T
Sift4G	Benign	0.31	T
Polyphen		0.0020	B
Vest4		0.070
MutPred		0.21		Loss of MoRF binding (P = 0.0363)
MVP		0.21
MPC		0.17
ClinPred		0.054	T
GERP RS		-11
Varity_R		0.033
gMVP		0.13
Mutation Taster		=91/9	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: rs375606736; hg19: chr10-101715231;