10-99929961-T-C

Variant names:

• chr10-99929961-T-C
• rs552702605
• NM_015221.4:c.2261-20815A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001318326.2(DNMBP):​c.803A>G​(p.Tyr268Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 702,916 control chromosomes in the GnomAD database, including 24 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 0.00062 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (23 hom.)
• Consequence: DNMBP NM_001318326.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.892
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045203567).
• BP6: Variant 10-99929961-T-C is Benign according to our data. Variant chr10-99929961-T-C is described in ClinVar as Benign. ClinVar VariationId is 3039087.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 23 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMBP	NM_015221.4	MANE Select	c.2261-20815A>G		intron	N/A	NP_056036.1	Q6XZF7-1
	DNMBP	NM_001318326.2		c.803A>G	p.Tyr268Cys	missense	Exon 1 of 14	NP_001305255.1	A0A1B0GTX1
	DNMBP	NM_001441287.1		c.2261-20815A>G		intron	N/A	NP_001428216.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNMBP	ENST00000324109.9	TSL:1 MANE Select	c.2261-20815A>G		intron	N/A	ENSP00000315659.4	Q6XZF7-1
	DNMBP	ENST00000636706.1	TSL:2	c.803A>G	p.Tyr268Cys	missense	Exon 1 of 14	ENSP00000489875.1	A0A1B0GTX1
	DNMBP	ENST00000856964.1		c.2261-20815A>G		intron	N/A	ENSP00000527023.1

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00251 AC: 337 AN: 134144 AF XY: 0.00335

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000697

Gnomad ASJ exome AF: 0.000241

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000285

Gnomad OTH exome AF: 0.000727

GnomAD4 exome AF: 0.00187 AC: 1027 AN: 550578 Hom.: 23 Cov.: 0 AF XY: 0.00255 AC XY: 760 AN XY: 298060

African (AFR) AF: 0.0000633 AC: 1 AN: 15792

American (AMR) AF: 0.000605 AC: 21 AN: 34702

Ashkenazi Jewish (ASJ) AF: 0.000250 AC: 5 AN: 20024

East Asian (EAS) AF: 0.0000311 AC: 1 AN: 32104

South Asian (SAS) AF: 0.0133 AC: 834 AN: 62700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33618

Middle Eastern (MID) AF: 0.00319 AC: 13 AN: 4076

European-Non Finnish (NFE) AF: 0.000363 AC: 115 AN: 316960

Other (OTH) AF: 0.00121 AC: 37 AN: 30602

GnomAD4 genome AF: 0.000617 AC: 94 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.000711 AC XY: 53 AN XY: 74498

African (AFR) AF: 0.000144 AC: 6 AN: 41580

American (AMR) AF: 0.000327 AC: 5 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68028

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.000336 Hom.: 0

Bravo AF: 0.000363

ExAC AF: 0.00731 AC: 118

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DNMBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.22
DANN	Benign	0.56
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0045	T
PhyloP100		-0.89
GERP RS		-4.8
Mutation Taster		=100/0	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: rs552702605; hg19: chr10-101689718;