rs2981804

Variant names:

• chr10-122574140-G-A
• rs2981804
• NM_001377530.1:c.283+378G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001377530.1(DMBT1):​c.283+378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,044 control chromosomes in the GnomAD database, including 18,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (18491 hom., cov: 33)
• Consequence: DMBT1 NM_001377530.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.675

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-122574140-G-A is Benign according to our data. Variant chr10-122574140-G-A is described in ClinVar as [Benign]. Clinvar id is 1225238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMBT1	NM_001377530.1	c.283+378G>A		intron_variant	Intron 6 of 55	ENST00000338354.10	NP_001364459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMBT1	ENST00000338354.10	c.283+378G>A		intron_variant	Intron 6 of 55	1	NM_001377530.1	ENSP00000342210.4

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73086 AN: 151926 Hom.: 18473 Cov.: 33

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.481 AC: 73136 AN: 152044 Hom.: 18491 Cov.: 33 AF XY: 0.483 AC XY: 35881 AN XY: 74322

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.504

Alfa AF: 0.518 Hom.: 4536

Bravo AF: 0.481

Asia WGS AF: 0.387 AC: 1347 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24223725) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs2981804; hg19: chr10-124333656;