chr13-71440659-T-C

Position:

• chr13-71440659-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_080759.6(DACH1):​c.2117A>G​(p.Tyr706Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DACH1 NM_080759.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72

Genes affected

DACH1 (HGNC:2663): (dachshund family transcription factor 1) This gene encodes a chromatin-associated protein that associates with other DNA-binding transcription factors to regulate gene expression and cell fate determination during development. The protein contains a Ski domain that is highly conserved from Drosophila to human. Expression of this gene is lost in some forms of metastatic cancer, and is correlated with poor prognosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACH1	NM_080759.6	c.2117A>G	p.Tyr706Cys	missense_variant	11/11	ENST00000613252.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACH1	ENST00000613252.5	c.2117A>G	p.Tyr706Cys	missense_variant	11/11	1	NM_080759.6	P2
DACH1	ENST00000619232.2	c.2273A>G	p.Tyr758Cys	missense_variant	12/12	5		A2
DACH1	ENST00000706274.1	c.1499A>G	p.Tyr500Cys	missense_variant	10/10
DACH1	ENST00000706275.1	c.1094A>G	p.Tyr365Cys	missense_variant	10/10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451914 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 722024

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.2123A>G (p.Y708C) alteration is located in exon 11 (coding exon 11) of the DACH1 gene. This alteration results from a A to G substitution at nucleotide position 2123, causing the tyrosine (Y) at amino acid position 708 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.68	D;D;D;D
MetaSVM	Benign	-0.75	T
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Pathogenic	0.88	D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.74
MVP		0.72
ClinPred		0.77	D
GERP RS		5.5
Varity_R		0.26
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-72014791;