rs2277244

Variant names:

• chr10-122599067-C-T
• rs2277244
• NM_001377530.1:c.3250C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001377530.1(DMBT1):​c.3250C>T​(p.His1084Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0339 in 1,613,808 control chromosomes in the GnomAD database, including 1,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.027 (85 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1172 hom.)
• Consequence: DMBT1 NM_001377530.1 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.34
• Publications: 11 publications found

Genes affected

DMBT1 (HGNC:2926): (deleted in malignant brain tumors 1) Loss of sequences from human chromosome 10q has been associated with the progression of human cancers. This gene was originally isolated based on its deletion in a medulloblastoma cell line. This gene is expressed with transcripts of 6.0, 7.5, and 8.0 kb in fetal lung and with one transcript of 8.0 kb in adult lung, although the 7.5 kb transcript has not been characterized. The encoded protein precursor is a glycoprotein containing multiple scavenger receptor cysteine-rich (SRCR) domains separated by SRCR-interspersed domains (SID). Transcript variant 2 (8.0 kb) has been shown to bind surfactant protein D independently of carbohydrate recognition. This indicates that DMBT1 may not be a classical tumor suppressor gene, but rather play a role in the interaction of tumor cells and the immune system. [provided by RefSeq, Mar 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030488968).
• BP6: Variant 10-122599067-C-T is Benign according to our data. Variant chr10-122599067-C-T is described in ClinVar as Benign. ClinVar VariationId is 3037168.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377530.1. 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
	DMBT1	NM_001377530.1	MANE Select	c.3250C>T	p.His1084Tyr	missense	Exon 26 of 56	NP_001364459.1	Q9UGM3-6
	DMBT1	NM_007329.3		c.3250C>T	p.His1084Tyr	missense	Exon 26 of 53	NP_015568.2	Q9UGM3-1
	DMBT1	NM_001320644.2		c.3250C>T	p.His1084Tyr	missense	Exon 26 of 53	NP_001307573.1	A0A590UJ76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBT1	ENST00000338354.10	TSL:1 MANE Select	c.3250C>T	p.His1084Tyr	missense	Exon 26 of 56	ENSP00000342210.4	Q9UGM3-6
	DMBT1	ENST00000344338.7	TSL:1	c.3220C>T	p.His1074Tyr	missense	Exon 25 of 52	ENSP00000343175.3	Q9UGM3-3
	DMBT1	ENST00000330163.8	TSL:1	c.1753C>T	p.His585Tyr	missense	Exon 16 of 40	ENSP00000327747.4	Q9UGM3-2

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4124 AN: 152160 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.00760

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0308

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.0401 AC: 9987 AN: 249032 AF XY: 0.0426

Gnomad AFR exome AF: 0.00659

Gnomad AMR exome AF: 0.0434

Gnomad ASJ exome AF: 0.0219

Gnomad EAS exome AF: 0.0793

Gnomad FIN exome AF: 0.0317

Gnomad NFE exome AF: 0.0314

Gnomad OTH exome AF: 0.0370

GnomAD4 exome AF: 0.0346 AC: 50546 AN: 1461530 Hom.: 1172 Cov.: 34 AF XY: 0.0358 AC XY: 26009 AN XY: 727054

African (AFR) AF: 0.00612 AC: 205 AN: 33472

American (AMR) AF: 0.0422 AC: 1887 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 519 AN: 26132

East Asian (EAS) AF: 0.0910 AC: 3612 AN: 39700

South Asian (SAS) AF: 0.0759 AC: 6544 AN: 86250

European-Finnish (FIN) AF: 0.0340 AC: 1817 AN: 53402

Middle Eastern (MID) AF: 0.0519 AC: 299 AN: 5762

European-Non Finnish (NFE) AF: 0.0302 AC: 33630 AN: 1111738

Other (OTH) AF: 0.0337 AC: 2033 AN: 60356

GnomAD4 genome AF: 0.0272 AC: 4135 AN: 152278 Hom.: 85 Cov.: 32 AF XY: 0.0284 AC XY: 2113 AN XY: 74454

African (AFR) AF: 0.00758 AC: 315 AN: 41560

American (AMR) AF: 0.0307 AC: 470 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3470

East Asian (EAS) AF: 0.0689 AC: 357 AN: 5178

South Asian (SAS) AF: 0.0819 AC: 395 AN: 4824

European-Finnish (FIN) AF: 0.0296 AC: 314 AN: 10604

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0308 AC: 2098 AN: 68018

Other (OTH) AF: 0.0299 AC: 63 AN: 2110

Alfa AF: 0.0263 Hom.: 23

Bravo AF: 0.0258

TwinsUK AF: 0.0297 AC: 110

ALSPAC AF: 0.0296 AC: 114

ESP6500AA AF: 0.00911 AC: 35

ESP6500EA AF: 0.0290 AC: 240

ExAC AF: 0.0410 AC: 4955

Asia WGS AF: 0.0790 AC: 277 AN: 3478

EpiCase AF: 0.0335

EpiControl AF: 0.0299

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DMBT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.42
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		4.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.30
MPC		0.058
ClinPred		0.091	T
GERP RS		3.6
PromoterAI		-0.032	Neutral
Varity_R		0.69
gMVP		0.21
Mutation Taster		=70/30	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2277244; hg19: chr10-124358583; COSMIC: COSV57545155;