3-183806890-C-T

Variant names:

• chr3-183806890-C-T
• rs752773736
• NM_018023.5:c.3809C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_018023.5(YEATS2):​c.3809C>T​(p.Ala1270Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1270G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: YEATS2 NM_018023.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

Genes affected

YEATS2 (HGNC:25489): (YEATS domain containing 2) Summary: The protein encoded by this gene is a scaffolding subunit of the ATAC complex, which is a complex with acetyltransferase activity on histones H3 and H4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2017]

YEATS2-AS1 (HGNC:41101): (YEATS2 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20799762).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YEATS2	NM_018023.5	c.3809C>T	p.Ala1270Val	missense_variant	Exon 28 of 31	ENST00000305135.10	NP_060493.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YEATS2	ENST00000305135.10	c.3809C>T	p.Ala1270Val	missense_variant	Exon 28 of 31	1	NM_018023.5	ENSP00000306983.5
YEATS2-AS1	ENST00000425008.3	n.2009G>A		non_coding_transcript_exon_variant	Exon 2 of 2	4
YEATS2	ENST00000472593.1	n.3237C>T		non_coding_transcript_exon_variant	Exon 2 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461720 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727168

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.064
Sift	Benign	0.046	D
Sift4G	Benign	0.14	T
Polyphen		0.79	P
Vest4		0.37
MutPred		0.17		Gain of glycosylation at S1268 (P = 0.02);
MVP		0.043
MPC		0.16
ClinPred		0.60	D
GERP RS		5.6
Varity_R		0.088
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs752773736; hg19: chr3-183524678;