rs200188202

Variant names:

• chr1-240493335-G-A
• NM_022469.4:c.141C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-240493335-G-A
• chr1-240493335-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_022469.4(GREM2):​c.141C>T​(p.His47His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: GREM2 NM_022469.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

Genes affected

GREM2 (HGNC:17655): (gremlin 2, DAN family BMP antagonist) This gene encodes a member of the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists contain cystine knots and typically form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which this gene belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted glycosylated protein encoded by this gene is likely due to its direct binding to BMP proteins. As an antagonist of BMP, this gene may play a role in regulating organogenesis, body patterning, and tissue differentiation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.107 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GREM2	NM_022469.4	c.141C>T	p.His47His	synonymous_variant	Exon 2 of 2	ENST00000318160.5	NP_071914.3
GREM2	XM_047427832.1	c.195C>T	p.His65His	synonymous_variant	Exon 3 of 3		XP_047283788.1
GREM2	XM_047427839.1	c.195C>T	p.His65His	synonymous_variant	Exon 4 of 4		XP_047283795.1
GREM2	XM_011544249.3	c.141C>T	p.His47His	synonymous_variant	Exon 3 of 3		XP_011542551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GREM2	ENST00000318160.5	c.141C>T	p.His47His	synonymous_variant	Exon 2 of 2	1	NM_022469.4	ENSP00000318650.4

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
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.6
DANN	Benign	0.90

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: chr1-240656635;