chr1-28743907-G-C

Position:

• chr1-28743907-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016258.3(YTHDF2):​c.1637G>C​(p.Ser546Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YTHDF2 NM_016258.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.15

Genes affected

YTHDF2 (HGNC:31675): (YTH N6-methyladenosine RNA binding protein F2) This gene encodes a member of the YTH (YT521-B homology) superfamily containing YTH domain. The YTH domain is typical for the eukaryotes and is particularly abundant in plants. The YTH domain is usually located in the middle of the protein sequence and may function in binding to RNA. In addition to a YTH domain, this protein has a proline rich region which may be involved in signal transduction. An Alu-rich domain has been identified in one of the introns of this gene, which is thought to be associated with human longevity. In addition, reciprocal translocations between this gene and the Runx1 (AML1) gene on chromosome 21 has been observed in patients with acute myeloid leukemia. This gene was initially mapped to chromosome 14, which was later turned out to be a pseudogene. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19520518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YTHDF2	NM_016258.3	c.1637G>C	p.Ser546Thr	missense_variant	4/5	ENST00000373812.8
YTHDF2	NM_001173128.2	c.1637G>C	p.Ser546Thr	missense_variant	5/6
YTHDF2	NM_001172828.2	c.1487G>C	p.Ser496Thr	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YTHDF2	ENST00000373812.8	c.1637G>C	p.Ser546Thr	missense_variant	4/5	1	NM_016258.3	P1
YTHDF2	ENST00000478283.5	n.2318G>C		non_coding_transcript_exon_variant	3/4	1
YTHDF2	ENST00000542507.5	c.1637G>C	p.Ser546Thr	missense_variant	5/6	5		P1
YTHDF2	ENST00000541996.5	c.1487G>C	p.Ser496Thr	missense_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	23
DANN	Benign	0.67
DEOGEN2	Benign	0.077	T;T;.
Eigen	Benign	0.032
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.77	T;.;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.78	N;N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.045
Sift	Benign	0.50	T;T;T
Sift4G	Benign	0.49	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.13
MutPred		0.42		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);.;
MVP		0.043
MPC		0.56
ClinPred		0.78	D
GERP RS		5.8
Varity_R		0.42
gMVP		0.27

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: chr1-29070419;