2-9598645-C-T

Variant names:

• chr2-9598645-C-T
• rs7569485
• NM_006826.4:c.295-7130G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006826.4(YWHAQ):​c.295-7130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,942 control chromosomes in the GnomAD database, including 28,313 homozygotes. 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: 𝑓 0.58 (28313 hom., cov: 31)
• Consequence: YWHAQ NM_006826.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• Publications: 4 publications found

Genes affected

YWHAQ (HGNC:12854): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta) This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse and rat orthologs. This gene is upregulated in patients with amyotrophic lateral sclerosis. It contains in its 5' UTR a 6 bp tandem repeat sequence which is polymorphic, however, there is no correlation between the repeat number and the disease. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006826.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAQ	NM_006826.4	MANE Select	c.295-7130G>A		intron	N/A	NP_006817.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAQ	ENST00000238081.8	TSL:1 MANE Select	c.295-7130G>A		intron	N/A	ENSP00000238081.3
	YWHAQ	ENST00000381844.8	TSL:1	c.295-7130G>A		intron	N/A	ENSP00000371267.4
	YWHAQ	ENST00000446619.1	TSL:3	c.295-7130G>A		intron	N/A	ENSP00000398990.1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88766 AN: 151824 Hom.: 28274 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.585 AC: 88859 AN: 151942 Hom.: 28313 Cov.: 31 AF XY: 0.573 AC XY: 42582 AN XY: 74272

African (AFR) AF: 0.811 AC: 33620 AN: 41462

American (AMR) AF: 0.432 AC: 6593 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2230 AN: 3468

East Asian (EAS) AF: 0.0600 AC: 310 AN: 5166

South Asian (SAS) AF: 0.385 AC: 1854 AN: 4814

European-Finnish (FIN) AF: 0.514 AC: 5407 AN: 10516

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36935 AN: 67942

Other (OTH) AF: 0.593 AC: 1249 AN: 2106

Alfa AF: 0.451 Hom.: 1905

Bravo AF: 0.587

Asia WGS AF: 0.298 AC: 1038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.40
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs7569485; hg19: chr2-9738774;