2-96186906-C-G

Position:

• chr2-96186906-C-G

Variant summary

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

The NM_020151.4(STARD7):​c.937G>C​(p.Asp313His) variant causes a missense change. 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: STARD7 NM_020151.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.98

Genes affected

STARD7 (HGNC:18063): (StAR related lipid transfer domain containing 7) Predicted to enable lipid binding activity. Predicted to act upstream of or within several processes, including establishment of skin barrier; mucociliary clearance; and myeloid dendritic cell activation. Predicted to be located in cytoplasm and extracellular region. Implicated in familial adult myoclonic epilepsy 2. [provided by Alliance of Genome Resources, Apr 2022]

STARD7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STARD7	NM_020151.4	c.937G>C	p.Asp313His	missense_variant	8/8	ENST00000337288.10	NP_064536.2
STARD7	NM_001385622.1	c.634G>C	p.Asp212His	missense_variant	8/8		NP_001372551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STARD7	ENST00000337288.10	c.937G>C	p.Asp313His	missense_variant	8/8	1	NM_020151.4	ENSP00000338030.5
STARD7	ENST00000462501.1	n.597G>C		non_coding_transcript_exon_variant	7/7	2
STARD7	ENST00000479456.1	n.910G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 14, 2022

The c.937G>C (p.D313H) alteration is located in exon 8 (coding exon 8) of the STARD7 gene. This alteration results from a G to C substitution at nucleotide position 937, causing the aspartic acid (D) at amino acid position 313 to be replaced by a histidine (H). 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
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.41		Gain of helix (P = 0.062);
MVP		0.35
MPC		1.7
ClinPred		0.98	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.80
gMVP		0.59

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: chr2-96852644;