2-137057202-A-G

Variant names:

• chr2-137057202-A-G
• NM_001316349.2:c.922A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001316349.2(THSD7B):​c.922A>G​(p.Arg308Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: THSD7B NM_001316349.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0930
• Publications: 0 publications found

Genes affected

THSD7B (HGNC:29348): (thrombospondin type 1 domain containing 7B) Predicted to be involved in actin cytoskeleton reorganization. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316349.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7B	NM_001316349.2	MANE Select	c.922A>G	p.Arg308Gly	missense	Exon 3 of 28	NP_001303278.1	Q9C0I4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THSD7B	ENST00000409968.6	TSL:5 MANE Select	c.922A>G	p.Arg308Gly	missense	Exon 3 of 28	ENSP00000387145.1	Q9C0I4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.98	T
PhyloP100		0.093
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.40
Sift	Benign	0.066	T
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.62		Loss of stability (P = 0.1315)
MVP		0.44
MPC		0.68
ClinPred		0.99	D
GERP RS		4.2
gMVP		0.75
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

hg19: chr2-137814772;