chr14-22575540-CA-C

Position:

• chr14-22575540-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001344.4(DAD1):​c.212-308del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 152,126 control chromosomes in the GnomAD database, including 1,181 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.092 (1181 hom., cov: 31)
• Consequence: DAD1 NM_001344.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57

Genes affected

DAD1 (HGNC:2664): (defender against cell death 1) DAD1, the defender against apoptotic cell death, was initially identified as a negative regulator of programmed cell death in the temperature sensitive tsBN7 cell line. The DAD1 protein disappeared in temperature-sensitive cells following a shift to the nonpermissive temperature, suggesting that loss of the DAD1 protein triggered apoptosis. DAD1 is believed to be a tightly associated subunit of oligosaccharyltransferase both in the intact membrane and in the purified enzyme, thus reflecting the essential nature of N-linked glycosylation in eukaryotes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-22575540-CA-C is Benign according to our data. Variant chr14-22575540-CA-C is described in ClinVar as [Benign]. Clinvar id is 1246596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAD1	NM_001344.4	c.212-308del		intron_variant		ENST00000250498.9	NP_001335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAD1	ENST00000250498.9	c.212-308del		intron_variant		1	NM_001344.4	ENSP00000250498	P1
DAD1	ENST00000538631.1	c.212-10404del		intron_variant		2		ENSP00000440242
DAD1	ENST00000543337.1	c.128-308del		intron_variant		3		ENSP00000440821
DAD1	ENST00000535847.1	c.123-308del		intron_variant, NMD_transcript_variant		2		ENSP00000442074

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13959 AN: 152008 Hom.: 1178 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0385

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0448

Gnomad OTH AF: 0.0888

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

GnomAD4 genome AF: 0.0920 AC: 13991 AN: 152126 Hom.: 1181 Cov.: 31 AF XY: 0.0896 AC XY: 6662 AN XY: 74390

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0527

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.0385

Gnomad4 NFE AF: 0.0448

Gnomad4 OTH AF: 0.0874

Alfa AF: 0.0751 Hom.: 107

Bravo AF: 0.0979

Asia WGS AF: 0.0250 AC: 90 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs11297491; hg19: chr14-23044440;