2-136990916-G-C

Variant names:

• chr2-136990916-G-C
• NM_001316349.2:c.140-65504G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001316349.2(THSD7B):​c.140-65504G>C variant causes a intron 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: THSD7B NM_001316349.2 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.427

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05891621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THSD7B	NM_001316349.2	c.140-65504G>C		intron_variant	Intron 2 of 27	ENST00000409968.6	NP_001303278.1
THSD7B	XM_047445935.1	c.-284-65504G>C		intron_variant	Intron 2 of 27		XP_047301891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THSD7B	ENST00000409968.6	c.140-65504G>C		intron_variant	Intron 2 of 27	5	NM_001316349.2	ENSP00000387145.1
THSD7B	ENST00000472720.5	n.*106-65504G>C		intron_variant	Intron 3 of 3	5		ENSP00000473349.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.25G>C (p.V9L) alteration is located in exon 1 (coding exon 1) of the THSD7B gene. This alteration results from a G to C substitution at nucleotide position 25, causing the valine (V) at amino acid position 9 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.92
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.094
Sift	Benign	0.16	T
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.27		Gain of ubiquitination at K13 (P = 0.1295);
MVP		0.014
ClinPred		0.036	T
GERP RS		-1.5

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: chr2-137748486;