2-137057146-A-G

Variant names:

• chr2-137057146-A-G
• rs377406339
• NM_001316349.2:c.866A>G

Variant summary

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

The NM_001316349.2(THSD7B):​c.866A>G​(p.His289Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict 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. H289P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: THSD7B NM_001316349.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

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

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=0.08944553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7B	NM_001316349.2	c.866A>G	p.His289Arg	missense_variant	Exon 3 of 28	ENST00000409968.6	NP_001303278.1
THSD7B	XM_047445935.1	c.443A>G	p.His148Arg	missense_variant	Exon 3 of 28		XP_047301891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD7B	ENST00000409968.6	c.866A>G	p.His289Arg	missense_variant	Exon 3 of 28	5	NM_001316349.2	ENSP00000387145.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461702 Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 727134

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T;.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.53	T;.;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.063
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.68	T;T;T
Polyphen		0.0040	.;.;B
Vest4		0.18
MutPred		0.44		Gain of MoRF binding (P = 0.0043);Gain of MoRF binding (P = 0.0043);.;
MVP		0.18
MPC		0.54
ClinPred		0.23	T
GERP RS		4.2
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs377406339; hg19: chr2-137814716; COSMIC: COSV105065761; COSMIC: COSV105065761;