rs2209172

Variant names:

• chr1-46512825-C-A
• rs2209172
• NM_172225.2:c.*331C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-46512825-C-A
• chr1-46512825-C-G
• chr1-46512825-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172225.2(DMBX1):​c.*331C>A variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DMBX1 NM_172225.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.996
• Publications: 0 publications found

Genes affected

DMBX1 (HGNC:19026): (diencephalon/mesencephalon homeobox 1) This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and may play a role in brain and sensory organ development. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DMBX1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172225.2. 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
	DMBX1	NM_172225.2	MANE Select	c.*331C>A		3_prime_UTR	Exon 6 of 6	NP_757379.1	Q8NFW5-2
	DMBX1	NM_001387776.1		c.*331C>A		3_prime_UTR	Exon 5 of 5	NP_001374705.1	Q8NFW5-1
	DMBX1	NM_147192.4		c.*331C>A		3_prime_UTR	Exon 6 of 6	NP_671725.1	Q8NFW5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBX1	ENST00000360032.4	TSL:1 MANE Select	c.*331C>A		3_prime_UTR	Exon 6 of 6	ENSP00000353132.3	Q8NFW5-2
	DMBX1	ENST00000928354.1		c.*331C>A		3_prime_UTR	Exon 5 of 5	ENSP00000598413.1
	DMBX1	ENST00000928355.1		c.*331C>A		3_prime_UTR	Exon 5 of 5	ENSP00000598414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 174036 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 88046

African (AFR) AF: 0.00 AC: 0 AN: 6568

American (AMR) AF: 0.00 AC: 0 AN: 7516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6436

East Asian (EAS) AF: 0.00 AC: 0 AN: 14408

South Asian (SAS) AF: 0.00 AC: 0 AN: 5988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 886

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 109854

Other (OTH) AF: 0.00 AC: 0 AN: 11526

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.2
DANN	Benign	0.80
PhyloP100		1.0

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: rs2209172; hg19: chr1-46978497;