chr2-216482762-G-T

Variant names:

• chr2-216482762-G-T
• rs763712548
• NM_014140.4:c.2650G>T

Variant summary

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

The NM_014140.4(SMARCAL1):​c.2650G>T​(p.Asp884Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SMARCAL1 NM_014140.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61

Genes affected

SMARCAL1 (HGNC:11102): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein shows sequence similarity to the E. coli RNA polymerase-binding protein HepA. Mutations in this gene are a cause of Schimke immunoosseous dysplasia (SIOD), an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency. [provided by RefSeq, Jul 2008]

RPL37A-DT (HGNC:40510): (RPL37A divergent transcript)

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 rank	MANE	Protein	UniProt
SMARCAL1	NM_014140.4	c.2650G>T	p.Asp884Tyr	missense_variant	Exon 18 of 18	ENST00000357276.9	NP_054859.2
SMARCAL1	NM_001127207.2	c.2650G>T	p.Asp884Tyr	missense_variant	Exon 18 of 18		NP_001120679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCAL1	ENST00000357276.9	c.2650G>T	p.Asp884Tyr	missense_variant	Exon 18 of 18	2	NM_014140.4	ENSP00000349823.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251292 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135806

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727228

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;T;T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Uncertain	2.7	M;M;.
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.98	D;D;.
Vest4		0.53
MutPred		0.48		Loss of disorder (P = 0.0394);Loss of disorder (P = 0.0394);.;
MVP		0.95
MPC		0.90
ClinPred		0.98	D
GERP RS		2.8
Varity_R		0.43
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs763712548; hg19: chr2-217347485;